Cell and Tissue Research

, Volume 349, Issue 3, pp 765–782 | Cite as

Kinases, phosphatases and proteases during sperm capacitation

  • Janetti Signorelli
  • Emilce S. Diaz
  • Patricio Morales


Fertilization is the process by which male and female haploid gametes (sperm and egg) unite to produce a genetically distinct individual. In mammals, fertilization involves a number of sequential steps, including sperm migration through the female genital tract, sperm penetration through the cumulus mass, sperm adhesion and binding to the zona pellucida, acrosome exocytosis, sperm penetration through the zona and fusion of the sperm and egg plasma membranes. However, freshly ejaculated sperm are not capable of fertilizing an oocyte. They must first undergo a series of biochemical and physiological changes, collectively known as capacitation, before acquiring fertilizing capabilities. Several molecules are required for successful capacitation and in vitro fertilization; these include bicarbonate, serum albumin (normally bovine serum albumin, BSA) and Ca2+. Bicarbonate activates the sperm protein soluble adenylyl cyclase (SACY), which results in increased levels of cAMP and cAMP-dependent protein kinase (PKA) activation. The response to bicarbonate is fast and cAMP levels increase within 60 s followed by an increase in PKA activity. Several studies with an anti-phospho-PKA substrate antibody have demonstrated a rapid increase in protein phosphorylation in human, mouse and boar sperm. The target proteins of PKA are not known and the precise role of BSA during capacitation is unclear. Most of the studies provide support for the idea that BSA acts by removing cholesterol from the sperm. The loss of cholesterol has been suggested to affect the bilayer of the sperm plasma membrane making it more fusogenic. The relationship between cholesterol loss and the activation of the cAMP/PKA pathway is also unclear. During early stages of capacitation, Ca2+ might be involved in the stimulation of SACY, although definitive proof is lacking. Protein tyrosine phosphorylation is another landmark of capacitation but occurs during the late stages of capacitation on a different time-scale from cAMP/PKA activation. Additionally, the tyrosine kinases present in sperm are not well characterized. Although protein phosphorylation depends upon the balanced action of protein kinases and protein phosphatase, we have even less information regarding the role of protein phosphatases during sperm capacitation. Over the last few years, several reports have pointed out that the ubiquitin-proteasome system might play a role during sperm capacitation, acrosome reaction and/or sperm-egg fusion. In the present review, we summarize the information regarding the role of protein kinases, phosphatases and the proteasome during sperm capacitation. Where appropriate, we give examples of the way that these molecules interact and regulate each other’s activities.


Sperm Capacitation Kinases Phosphatases Proteasome 


  1. Adachi J, Tate S, Miyake M, Harayama H (2008) Effects of protein phosphatase inhibitor calyculin A on the postacrosomal protein serine/threonine phosphorylation state and acrosome reaction in boar spermatozoa incubated with a cAMP analog. J Reprod Dev 54:171–176PubMedCrossRefGoogle Scholar
  2. Ahmad K, Bracho GE, Wolf DP, Tash JS (1995) Regulation of human sperm motility and hyperactivation components by calcium, calmodulin, and protein phosphatases. Arch Androl 35:187–208PubMedCrossRefGoogle Scholar
  3. Aitken A (2006) 14-3-3 proteins: a historic overview. Semin Cancer Biol 16:162–172PubMedCrossRefGoogle Scholar
  4. Alnagar FA, Brennan P, Brewis IA (2010) Bicarbonate-dependent serine/threonine protein dephosphorylation in capacitating boar spermatozoa. J Androl 31:393–405PubMedCrossRefGoogle Scholar
  5. Alonso A, Sasin J, Bottini N, Friedberg I, Friedberg I, Osterman A, Godzik A, Hunter T, Dixon J, Mustelin T (2004) Protein tyrosine phosphatases in the human genome. Cell 117:699–711PubMedCrossRefGoogle Scholar
  6. Andreeva AV, Kutuzov MA (2009) PPEF/PP7 protein Ser/Thr phosphatases. Cell Mol Life Sci 66:3103-3110PubMedCrossRefGoogle Scholar
  7. Arcelay E, Salicioni AM, Wertheimer E, Visconti PE (2008) Identification of proteins undergoing tyrosine phosphorylation during mouse sperm capacitation. Int J Dev Biol 52:463–472PubMedCrossRefGoogle Scholar
  8. Asai M, Tsukamoto O, Minamino T, Asanuma H, Fujita M, Asano Y, Takahama H, Sasaki H, Higo S, Asakura M, Takashima S, Hori M, Kitakaze M (2009) PKA rapidly enhances proteasome assembly and activity in in vivo canine hearts. J Mol Cell Cardiol 46:452–462PubMedCrossRefGoogle Scholar
  9. Ashizawa K, Wishart GJ, Nakao H, Okino Y, Tsuzuki Y (1994) Inhibition of temperature-dependent immobilization of fowl spermatozoa at body temperature by an increased intracellular pH. J Reprod Fertil 101:593–598PubMedCrossRefGoogle Scholar
  10. Ashizawa K, Wishart GJ, Ranasinghe AR, Katayama S, Tsuzuki Y (2004) Protein phosphatase-type 2B is involved in the regulation of the acrosome reaction but not in the temperature-dependent flagellar movement of fowl spermatozoa. Reproduction 128:783–787PubMedCrossRefGoogle Scholar
  11. Ashizawa K, Wishart GJ, Katayama S, Takano D, Ranasinghe AR, Narumi K, Tsuzuki Y (2006) Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A. Reproduction 131:1017–1024PubMedCrossRefGoogle Scholar
  12. Austin CR (1951) Observations on the penetration of the sperm in the mammalian egg. Aust J Sci Res B 4:581–596PubMedGoogle Scholar
  13. Bailey JL (2010) Factors regulating sperm capacitation. Syst Biol Reprod Med 56:334–348PubMedCrossRefGoogle Scholar
  14. Baker MA, Hetherington L, Aitken RJ (2006) Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa. J Cell Sci 119:3182–3192PubMedCrossRefGoogle Scholar
  15. Baker MA, Reeves G, Hetherington L, Muller J, Baur I, Aitken RJ (2007) Identification of gene products present in Triton X-100 soluble and insoluble fractions of human spermatozoa lysates using LC-MS/MS analysis. Proteomics Clin Appl 1:524–532PubMedCrossRefGoogle Scholar
  16. Baker MA, Hetherington L, Reeves G, Muller J, Aitken RJ (2008) The rat sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification. Proteomics 8:2312–2321PubMedCrossRefGoogle Scholar
  17. Baker MA, Hetherington L, Curry B, Aitken RJ (2009) Phosphorylation and consequent stimulation of the tyrosine kinase c-Abl by PKA in mouse spermatozoa; its implications during capacitation. Dev Biol 333:57–66PubMedCrossRefGoogle Scholar
  18. Barford D, Das AK, Egloff MP (1998) The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annu Rev Biophys Biomol Struct 27:133–164PubMedCrossRefGoogle Scholar
  19. Barua M, Bhattacharyya U, Majumder GC (1985) Occurrence of an ecto-phosphoprotein phosphatase in goat epididymal spermatozoa. Biochem Int 10:733–741PubMedGoogle Scholar
  20. Bastians H, Ponstingl H (1996) The novel human protein serine/threonine phosphatase 6 is a functional homologue of budding yeast Sit4p and fission yeast pp e1, which are involved in cell cycle regulation. J Cell Sci 109:2865–2874PubMedGoogle Scholar
  21. Becker W, Kentrup H, Klumpp S, Schultz JE, Joost HG (1994) Molecular cloning of a protein serine/threonine phosphatase containing a putative regulatory tetratricopeptide repeat domain. J Biol Chem 269:22586–22592PubMedGoogle Scholar
  22. Bedford L, Paine S, Sheppard PW, Mayer RJ, Roelofs J (2010) Assembly, structure, and function of the 26S proteasome. Trends Cell Biol 20:391–401PubMedCrossRefGoogle Scholar
  23. Bedu-Addo K, Lefievre L, Moseley FL, Barratt CL, Publicover SJ (2005) Bicarbonate and bovine serum albumin reversibly “switch” capacitation-induced events in human spermatozoa. Mol Hum Reprod 11:683–691PubMedCrossRefGoogle Scholar
  24. Bialy LP, Ziemba HT, Marianowski P, Fracki S, Bury M, Wójcik C (2001) Localization of a proteasomal antigen in human spermatozoa: immunohistochemical electron microscopic study. Folia Histochem Cytobiol 39:129–130PubMedGoogle Scholar
  25. Bose S, Mason GG, Rivett AJ (1999) Phosphorylation of proteasomes in mammalian cells. Mol Biol Rep 26:11–14PubMedCrossRefGoogle Scholar
  26. Breitbart H, Naor Z (1999) Protein kinases in mammalian sperm capacitation and the acrosome reaction. Rev Reprod 4:151–159PubMedCrossRefGoogle Scholar
  27. Brewis ND, Street AJ, Prescott AR, Cohen PT (1993) PPX, a novel protein serine/threonine phosphatase localized to centrosomes. EMBO J 12:987–996PubMedGoogle Scholar
  28. Brush MH, Shenolikar S (2008) Control of cellular GADD34 levels by the 26S proteasome. Mol Cell Biol 28:6989–7000PubMedCrossRefGoogle Scholar
  29. Buffone MG, Verstraeten SV, Calamera JC, Doncel GF (2009) High cholesterol content and decreased membrane fluidity in human spermatozoa are associated with protein tyrosine phosphorylation and functional deficiencies. J Androl 30:552–558PubMedCrossRefGoogle Scholar
  30. Carrera A, Moos J, Ning XP, Gerton GL, Tesarik J, Kopf GS, Moss SB (1996) Regulation of protein tyrosine phosphorylation in human sperm by a calcium/calmodulin-dependent mechanism: identification of A kinase anchor proteins as major substrates for tyrosine phosphorylation. Dev Biol 180:284–296PubMedCrossRefGoogle Scholar
  31. Chakrabarti R, Cheng L, Puri P, Soler D, Vijayaraghavan S (2007a) Protein phosphatase PP1 gamma 2 in sperm morphogenesis and epididymal initiation of sperm motility. Asian J Androl 9:445–452PubMedCrossRefGoogle Scholar
  32. Chakrabarti R, Kline D, Lu J, Orth J, Pilder S, Vijayaraghavan S (2007b) Analysis of Ppp 1cc-null mice suggests a role for PP1gamma2 in sperm morphogenesis. Biol Reprod 76:992–1001PubMedCrossRefGoogle Scholar
  33. Chang CD, Mukai H, Kuno T, Tanaka C (1994) cDNA cloning of an alternatively spliced isoform of the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase (calcineurin B alpha 2). Biochim Biophys Acta 1217:174–180PubMedCrossRefGoogle Scholar
  34. Chang MC (1951) Fertilizing capacity of spermatozoa deposited into the Fallopian tubes. Nature 168:697–698PubMedCrossRefGoogle Scholar
  35. Chinkers M (1994) Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor. Proc Natl Acad Sci USA 91:11075–11079PubMedCrossRefGoogle Scholar
  36. Choi BH, Hur EM, Lee JH, Jun DJ, Kim KT (2006) Protein kinase Cdelta-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death. J Cell Sci 119:1329–1340PubMedCrossRefGoogle Scholar
  37. Ciechanover A (1998) The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J 17:7151–7160PubMedCrossRefGoogle Scholar
  38. Ciechanover A (2005a) Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Cell Death Differ 12:1178–1190PubMedCrossRefGoogle Scholar
  39. Ciechanover A (2005b) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6:79–87PubMedCrossRefGoogle Scholar
  40. Ciechanover A (2006) The ubiquitin proteolytic system: from a vague idea, through basic mechanisms, and onto human diseases and drug targeting. Neurology 66:S7–19PubMedCrossRefGoogle Scholar
  41. Cohen P (1989) The structure and regulation of protein phosphatases. Annu Rev Biochem 58:453–508PubMedCrossRefGoogle Scholar
  42. Cohen PT (1997) Novel protein serine/threonine phosphatases: variety is the spice of life. Trends Biochem Sci 22:245–251PubMedCrossRefGoogle Scholar
  43. Cohen PT (2002) Protein phosphatase 1–targeted in many directions. J Cell Sci 115:241–256PubMedGoogle Scholar
  44. Cohen PT, Brewis ND, Hughes V, Mann DJ (1990) Protein serine/threonine phosphatases; an expanding family. FEBS Lett 268:355–359PubMedCrossRefGoogle Scholar
  45. Cross NL (2004) Reorganization of lipid rafts during capacitation of human sperm. Biol Reprod 71:1367–1373PubMedCrossRefGoogle Scholar
  46. Demarco IA, Espinosa F, Edwards J, Sosnik J, De La Vega-Beltran JL, Hockensmith JW, Kopf GS, Darszon A, Visconti PE (2003) Involvement of a Na+/HCO3 - cotransporter in mouse sperm capacitation. J Biol Chem 278:7001–7009PubMedCrossRefGoogle Scholar
  47. Diaz ES, Kong M, Morales P (2007) Effect of fibronectin on proteasome activity, acrosome reaction, tyrosine phosphorylation and intracellular calcium concentrations of human sperm. Hum Reprod 22:1420–1430PubMedCrossRefGoogle Scholar
  48. Dickinson RJ, Keyse SM (2006) Diverse physiological functions for dual-specificity MAP kinase phosphatases. J Cell Sci 119:4607–4615PubMedCrossRefGoogle Scholar
  49. Esposito G, Jaiswal BS, Xie F, Krajnc-Franken MA, Robben TJ, Strik AM, Kuil C, Philipsen RL, Duin M van, Conti M, Gossen JA (2004) Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proc Natl Acad Sci USA 101:2993–2998PubMedCrossRefGoogle Scholar
  50. Fardilha M, Esteves SL, Korrodi-Gregorio L, Pelech S, Cruz e Silva OA da, Cruz e Silva E da (2011) Protein phosphatase 1 complexes modulate sperm motility and present novel targets for male infertility. Mol Hum Reprod 17:466–477PubMedCrossRefGoogle Scholar
  51. Ficarro S, Chertihin O, Westbrook VA, White F, Jayes F, Kalab P, Marto JA, Shabanowitz J, Herr JC, Hunt DF, Visconti PE (2003) Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation. J Biol Chem 278:11579–11589PubMedCrossRefGoogle Scholar
  52. Fischer KA, Van Leyen K, Lovercamp KW, Manandhar G, Sutovsky M, Feng D, Safranski T, Sutovsky P (2005) 15-Lipoxygenase is a component of the mammalian sperm cytoplasmic droplet. Reproduction 130:213–222PubMedCrossRefGoogle Scholar
  53. Fisher HM, Brewis IA, Barratt CL, Cooke ID, Moore HD (1998) Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation. Mol Hum Reprod 4:849–855PubMedCrossRefGoogle Scholar
  54. Furuya S, Endo Y, Oba M, Nozawa S, Suzuki S (1992) Effects of modulators of protein kinases and phosphatases on mouse sperm capacitation. J Assist Reprod Genet 9:391–399PubMedCrossRefGoogle Scholar
  55. Furuya S, Endo Y, Osumi K, Oba M, Nozawa S, Suzuki S (1993) Calyculin A, protein phosphatase inhibitor, enhances capacitation of human sperm. Fertil Steril 59:216–222PubMedGoogle Scholar
  56. Gadella BM, Harrison RA (2000) The capacitating agent bicarbonate induces protein kinase A-dependent changes in phospholipid transbilayer behavior in the sperm plasma membrane. Development 127:2407–2420PubMedGoogle Scholar
  57. Gallastegui N, Groll M (2010) The 26S proteasome: assembly and function of a destructive machine. Trends Biochem Sci 35:634–642PubMedCrossRefGoogle Scholar
  58. Gallego M, Virshup DM (2005) Protein serine/threonine phosphatases: life, death, and sleeping. Curr Opin Cell Biol 17:197–202PubMedCrossRefGoogle Scholar
  59. Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82:373–428PubMedGoogle Scholar
  60. Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426:895–899PubMedCrossRefGoogle Scholar
  61. Goto N, Harayama H (2009) Calyculin A-sensitive protein phosphatases are involved in maintenance of progressive movement in mouse spermatozoa in vitro by suppression of autophosphorylation of protein kinase A. J Reprod Dev 55:327–334PubMedCrossRefGoogle Scholar
  62. Groll M, Koguchi Y, Huber R, Kohno J (2001) Crystal structure of the 20 S proteasome:TMC-95A complex: a non-covalent proteasome inhibitor. J Mol Biol 311:543–548PubMedCrossRefGoogle Scholar
  63. Han Y, Haines CJ, Feng HL (2007) Role(s) of the serine/threonine protein phosphatase 1 on mammalian sperm motility. Arch Androl 53:169–177PubMedCrossRefGoogle Scholar
  64. Haraguchi CM, Mabuchi T, Hirata S, Shoda T, Tokumoto T, Hoshi K, Yokota S (2007) Possible function of caudal nuclear pocket: degradation of nucleoproteins by ubiquitin-proteasome system in rat spermatids and human sperm. J Histochem Cytochem 55:585–595PubMedCrossRefGoogle Scholar
  65. Harayama H (2003) Viability and protein phosphorylation patterns of boar spermatozoa agglutinated by treatment with a cell-permeable cyclic adenosine 3′,5′-monophosphate analog. J Androl 24:831–842PubMedGoogle Scholar
  66. Harayama H, Nakamura K (2008) Changes of PKA and PDK1 in the principal piece of boar spermatozoa treated with a cell-permeable cAMP analog to induce flagellar hyperactivation. Mol Reprod Dev 75:1396–1407PubMedCrossRefGoogle Scholar
  67. Harrison RA (2004) Rapid PKA-catalysed phosphorylation of boar sperm proteins induced by the capacitating agent bicarbonate. Mol Reprod Dev 67:337–352PubMedCrossRefGoogle Scholar
  68. Harrison RA, Miller NG (2000) cAMP-dependent protein kinase control of plasma membrane lipid architecture in boar sperm. Mol Reprod Dev 55:220–228PubMedCrossRefGoogle Scholar
  69. Hershko A (2005) The ubiquitin system for protein degradation and some of its roles in the control of the cell-division cycle (Nobel lecture). Angew Chem Int Ed Engl 44:5932–5943PubMedCrossRefGoogle Scholar
  70. Hess KC, Jones BH, Marquez B, Chen Y, Ord TS, Kamenetsky M, Miyamoto C, Zippin JH, Kopf GS, Suarez SS, Levin LR, Williams CJ, Buck J, Moss SB (2005) The "soluble" adenylyl cyclase in sperm mediates multiple signaling events required for fertilization. Dev Cell 9:249–259PubMedCrossRefGoogle Scholar
  71. Hicke L, Dunn R (2003) Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol 19:141–172PubMedCrossRefGoogle Scholar
  72. Honkanen RE, Golden T (2002) Regulators of serine/threonine protein phosphatases at the dawn of a clinical era? Curr Med Chem 9:2055–2075PubMedGoogle Scholar
  73. Hoskins DD, Acott TS, Critchlow L, Vijayaraghavan S (1983) Studies on the roles of cyclic AMP and calcium in the development of bovine sperm motility. J Submicrosc Cytol 15:21–27PubMedGoogle Scholar
  74. Hu MC, Tang-Oxley Q, Qiu WR, Wang YP, Mihindukulasuriya KA, Afshar R, Tan TH (1998) Protein phosphatase X interacts with c-Rel and stimulates c-Rel/nuclear factor kappaB activity. J Biol Chem 273:33561–33565PubMedCrossRefGoogle Scholar
  75. Hu MC, Shui JW, Mihindukulasuriya KA, Tan TH (2001) Genomic structure of the mouse PP4 gene: a developmentally regulated protein phosphatase. Gene 278:89–99PubMedCrossRefGoogle Scholar
  76. Huang X, Honkanen RE (1998) Molecular cloning, expression, and characterization of a novel human serine/threonine protein phosphatase, PP7, that is homologous to Drosophila retinal degeneration C gene product (rdgC). J Biol Chem 273:1462–1468PubMedCrossRefGoogle Scholar
  77. Huang X, Cheng A, Honkanen RE (1997) Genomic organization of the human PP4 gene encoding a serine/threonine protein phosphatase (PP4) suggests a common ancestry with PP2A. Genomics 44:336–343PubMedCrossRefGoogle Scholar
  78. Huang YH, Kuo SP, Lin MH, Shih CM, Chu ST, Wei CC, Wu TJ, Chen YH (2005) Signals of seminal vesicle autoantigen suppresses bovine serum albumin-induced capacitation in mouse sperm. Biochem Biophys Res Commun 338:1564-1571PubMedCrossRefGoogle Scholar
  79. Huang Z, Khatra B, Bollen M, Carr DW, Vijayaraghavan S (2002) Sperm PP1gamma2 is regulated by a homologue of the yeast protein phosphatase binding protein sds22. Biol Reprod 67:1936–1942PubMedCrossRefGoogle Scholar
  80. Hunter T (1995) Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80:225–236PubMedCrossRefGoogle Scholar
  81. Ingebritsen TS, Cohen P (1983) Protein phosphatases: properties and role in cellular regulation. Science 221:331–338PubMedCrossRefGoogle Scholar
  82. Janssens V, Goris J (2001) Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J 353:417–439PubMedCrossRefGoogle Scholar
  83. Jin M, Fujiwara E, Kakiuchi Y, Okabe M, Satouh Y, Baba SA, Chiba K, Hirohashi N (2011) Most fertilizing mouse spermatozoa begin their acrosome reaction before contact with the zona pellucida during in vitro fertilization. Proc Natl Acad Sci USA 108:4892–4896PubMedCrossRefGoogle Scholar
  84. Kajino T, Ren H, Iemura S, Natsume T, Stefansson B, Brautigan DL, Matsumoto K, Ninomiya-Tsuji J (2006) Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway. J Biol Chem 281:39891–39896PubMedCrossRefGoogle Scholar
  85. Khew-Goodall Y, Hemmings BA(1988) Tissue-specific expression of mRNAs encoding alpha- and beta-catalytic subunits of protein phosphatase 2A. FEBS Lett 238:265–268PubMedCrossRefGoogle Scholar
  86. Kitagawa Y, Sasaki K, Shima H, Shibuya M, Sugimura T, Nagao M (1990) Protein phosphatases possibly involved in rat spermatogenesis. Biochem Biophys Res Commun 171:230–235PubMedCrossRefGoogle Scholar
  87. Kloeker S, Reed R, McConnell JL, Chang D, Tran K, Westphal RS, Law BK, Colbran RJ, Kamoun M, Campbell KS, Wadzinski BE (2003) Parallel purification of three catalytic subunits of the protein serine/threonine phosphatase 2A family (PP2A(C), PP4(C), and PP6(C)) and analysis of the interaction of PP2A(C) with alpha4 protein. Protein Expr Purif 31:19–33PubMedCrossRefGoogle Scholar
  88. Kondoh K, Nishida E (2007) Regulation of MAP kinases by MAP kinase phosphatases. Biochim Biophys Acta 1773:1227–1237PubMedCrossRefGoogle Scholar
  89. Kong M, Diaz ES, Morales P (2009) Participation of the human sperm proteasome in the capacitation process and its regulation by protein kinase A and tyrosine kinase. Biol Reprod 80:1026–1035PubMedCrossRefGoogle Scholar
  90. Krapf D, Arcelay E, Wertheimer EV, Sanjay A, Pilder SH, Salicioni AM, Visconti PE (2010) Inhibition of Ser/Thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors. J Biol Chem 285:7977–7985PubMedCrossRefGoogle Scholar
  91. Lalancette C, Faure RL, Leclerc P (2006) Identification of the proteins present in the bull sperm cytosolic fraction enriched in tyrosine kinase activity: a proteomic approach. Proteomics 6:4523–4540PubMedCrossRefGoogle Scholar
  92. Lax Y, Rubinstein S, Breitbart H (1994) Epidermal growth factor induces acrosomal exocytosis in bovine sperm. FEBS Lett 339:234–238PubMedCrossRefGoogle Scholar
  93. Leclerc P, Goupil S (2002) Regulation of the human sperm tyrosine kinase c-yes. Activation by cyclic adenosine 3′,5′-monophosphate and inhibition by Ca2+. Biol Reprod 67:301–307PubMedCrossRefGoogle Scholar
  94. Leclerc P, Lamirande E de, Gagnon C (1996) Cyclic adenosine 3′,5′monophosphate-dependent regulation of protein tyrosine phosphorylation in relation to human sperm capacitation and motility. Biol Reprod 55:684–692PubMedCrossRefGoogle Scholar
  95. Leclerc P, Lamirande E de, Gagnon C (1998) Interaction between Ca2+, cyclic 3′,5′ adenosine monophosphate, the superoxide anion, and tyrosine phosphorylation pathways in the regulation of human sperm capacitation. J Androl 19:434–443PubMedGoogle Scholar
  96. Lee TH, Solomon MJ, Mumby MC, Kirschner MW (1991) INH, a negative regulator of MPF, is a form of protein phosphatase 2A. Cell 64:415–423PubMedCrossRefGoogle Scholar
  97. Liauw S, Steinberg RA (1996) Dephosphorylation of catalytic subunit of cAMP-dependent protein kinase at Thr-197 by a cellular protein phosphatase and by purified protein phosphatase-2A. J Biol Chem 271:258–263PubMedCrossRefGoogle Scholar
  98. Liu DY, Clarke GN, Baker HW (2006) Tyrosine phosphorylation on capacitated human sperm tail detected by immunofluorescence correlates strongly with sperm-zona pellucida (ZP) binding but not with the ZP-induced acrosome reaction. Hum Reprod 21:1002–1008PubMedCrossRefGoogle Scholar
  99. Luconi M, Barni T, Vannelli GB, Krausz C, Marra F, Benedetti PA, Evangelista V, Francavilla S, Properzi G, Forti G, Baldi E (1998a) Extracellular signal-regulated kinases modulate capacitation of human spermatozoa. Biol Reprod 58:1476–1489PubMedCrossRefGoogle Scholar
  100. Luconi M, Krausz C, Barni T, Vannelli GB, Forti G, Baldi E (1998b) Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in human spermatozoa. Mol Hum Reprod 4:251–258PubMedCrossRefGoogle Scholar
  101. Marchetti S, Gimond C, Chambard JC, Touboul T, Roux D, Pouyssegur J, Pages G (2005) Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation. Mol Cell Biol 25:854–864PubMedCrossRefGoogle Scholar
  102. Marino R, De Santis R, Hirohashi N, Hoshi M, Pinto MR, Usui N (1992) Purification and characterization of a vitelline coat lysin from Ciona intestinalis spermatozoa. Mol Reprod Dev 32:383–388PubMedCrossRefGoogle Scholar
  103. Martinez-Heredia J, Mateo S de, Vidal-Taboada JM, Ballesca JL, Oliva R (2008) Identification of proteomic differences in asthenozoospermic sperm samples. Hum Reprod 23:783–791PubMedCrossRefGoogle Scholar
  104. Mason GG, Hendil KB, Rivett AJ (1996) Phosphorylation of proteasomes in mammalian cells. Identification of two phosphorylated subunits and the effect of phosphorylation on activity. Eur J Biochem 238:453–462PubMedCrossRefGoogle Scholar
  105. Mason GG, Murray RZ, Pappin D, Rivett AJ (1998) Phosphorylation of ATPase subunits of the 26S proteasome. FEBS Lett 430:269–274PubMedCrossRefGoogle Scholar
  106. Matsumura K, Aketa K (1991) Proteasome (multicatalytic proteinase) of sea urchin sperm and its possible participation in the acrosome reaction. Mol Reprod Dev 29:189–199PubMedCrossRefGoogle Scholar
  107. Millward TA, Zolnierowicz S, Hemmings BA (1999) Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci 24:186–191PubMedCrossRefGoogle Scholar
  108. Mishra S, Somanath PR, Huang Z, Vijayaraghavan S (2003) Binding and inactivation of the germ cell-specific protein phosphatase PP1gamma2 by sds22 during epididymal sperm maturation. Biol Reprod 69:1572–1579PubMedCrossRefGoogle Scholar
  109. Mitchell LA, Nixon B, Baker MA, Aitken RJ (2008) Investigation of the role of SRC in capacitation-associated tyrosine phosphorylation of human spermatozoa. Mol Hum Reprod 14:235–243PubMedCrossRefGoogle Scholar
  110. Moller SG, Kim YS, Kunkel T, Chua NH (2003) PP7 is a positive regulator of blue light signaling in Arabidopsis. Plant Cell 15:1111–1119PubMedCrossRefGoogle Scholar
  111. Morales P, Kong M, Pizarro E, Pasten C (2003) Participation of the sperm proteasome in human fertilization. Hum Reprod 18:1010–1017PubMedCrossRefGoogle Scholar
  112. Morales P, Pizarro E, Kong M, Jara M (2004) Extracellular localization of proteasomes in human sperm. Mol Reprod Dev 68:115–124PubMedCrossRefGoogle Scholar
  113. Morales P, Diaz ES, Kong M (2007) Proteasome activity and its relationship with protein phosphorylation during capacitation and acrosome reaction in human spermatozoa. Soc Reprod Fertil Suppl 65:269–273PubMedGoogle Scholar
  114. Morgan DJ, Weisenhaus M, Shum S, Su T, Zheng R, Zhang C, Shokat KM, Hille B, Babcock DF, McKnight GS (2008) Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation. Proc Natl Acad Sci USA 105:20740–20745PubMedCrossRefGoogle Scholar
  115. Mourtada-Maarabouni M, Kirkham L, Jenkins B, Rayner J, Gonda TJ, Starr R, Trayner I, Farzaneh F, Williams GT (2003) Functional expression cloning reveals proapoptotic role for protein phosphatase 4. Cell Death Differ 10:1016–1024PubMedCrossRefGoogle Scholar
  116. Muramatsu T, Giri PR, Higuchi S, Kincaid RL (1992) Molecular cloning of a calmodulin-dependent phosphatase from murine testis: identification of a developmentally expressed nonneural isoenzyme. Proc Natl Acad Sci USA 89:529–533PubMedCrossRefGoogle Scholar
  117. Muratori M, Marchiani S, Tamburrino L, Forti G, Luconi M, Baldi E (2011) Markers of human sperm functions in the ICSI era. Front Biosci 16:1344–1363PubMedCrossRefGoogle Scholar
  118. Naaby-Hansen S, Mandal A, Wolkowicz MJ, Sen B, Westbrook VA, Shetty J, Coonrod SA, Klotz KL, Kim YH, Bush LA, Flickinger CJ, Herr JC (2002) CABYR, a novel calcium-binding tyrosine phosphorylation-regulated fibrous sheath protein involved in capacitation. Dev Biol 242:236–254PubMedCrossRefGoogle Scholar
  119. Nakamura K, Lazari MF, Li S, Korgaonkar C, Ascoli M (1999) Role of the rate of internalization of the agonist-receptor complex on the agonist-induced down-regulation of the lutropin/choriogonadotropin receptor. Mol Endocrinol 13:1295–1304PubMedCrossRefGoogle Scholar
  120. Nalepa G, Rolfe M, Harper JW (2006) Drug discovery in the ubiquitin-proteasome system. Nat Rev Drug Discov 5:596–613PubMedCrossRefGoogle Scholar
  121. Nass SJ, Strauss JF (eds) (2004) New frontiers in contraceptive research: a blueprint for action. National Academy, Washington, D.C.Google Scholar
  122. Naz RK (1998) c-Abl proto-oncoprotein is expressed and tyrosine phosphorylated in human sperm cell. Mol Reprod Dev 51:210–217PubMedCrossRefGoogle Scholar
  123. Naz RK (1999) Involvement of protein serine and threonine phosphorylation in human sperm capacitation. Biol Reprod 60:1402–1409PubMedCrossRefGoogle Scholar
  124. Naz RK, Rajesh PB (2004) Role of tyrosine phosphorylation in sperm capacitation/acrosome reaction. Reprod Biol Endocrinol 2:75PubMedCrossRefGoogle Scholar
  125. Naz RK, Ahmad K, Kumar R (1991) Role of membrane phosphotyrosine proteins in human spermatozoal function. J Cell Sci 99:157–165PubMedGoogle Scholar
  126. Naz RK, Ahmad K, Kaplan P (1992) Expression and function of ras proto-oncogene proteins in human sperm cells. J Cell Sci 102:487–494PubMedGoogle Scholar
  127. Nolan MA, Babcock DF, Wennemuth G, Brown W, Burton KA, McKnight GS (2004) Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility. Proc Natl Acad Sci USA 101:13483–13488PubMedCrossRefGoogle Scholar
  128. Pardo PS, Murray PF, Walz K, Franco L, Passeron S (1998) In vivo and in vitro phosphorylation of the alpha 7/PRS1 subunit of Saccharomyces cerevisiae 20 S proteasome: in vitro phosphorylation by protein kinase CK2 is absolutely dependent on polylysine. Arch Biochem Biophys 349:397–401PubMedCrossRefGoogle Scholar
  129. Pariset C, Weinman S (1994) Differential localization of two isoforms of the regulatory subunit RII alpha of cAMP-dependent protein kinase in human sperm: biochemical and cytochemical study. Mol Reprod Dev 39:415–422PubMedCrossRefGoogle Scholar
  130. Pasten C, Morales P, Kong M (2005) Role of the sperm proteasome during fertilization and gamete interaction in the mouse. Mol Reprod Dev 71:209–219PubMedCrossRefGoogle Scholar
  131. Pinto MR, Hoshi M, Marino R, Amoroso A, De Santis R (1990) Chymotrypsin-like enzymes are involved in sperm penetration through the vitelline coat of Ciona intestinalis egg. Mol Reprod Dev 26:319–323PubMedCrossRefGoogle Scholar
  132. Pizarro E, Pasten C, Kong M, Morales P (2004) Proteasomal activity in mammalian spermatozoa. Mol Reprod Dev 69:87–93PubMedCrossRefGoogle Scholar
  133. Puri P, Myers K, Kline D, Vijayaraghavan S (2008) Proteomic analysis of bovine sperm YWHA binding partners identify proteins involved in signaling and metabolism. Biol Reprod 79:1183–1191PubMedCrossRefGoogle Scholar
  134. Rawe VY, Diaz ES, Abdelmassih R, Wojcik C, Morales P, Sutovsky P, Chemes HE (2008) The role of sperm proteasomes during sperm aster formation and early zygote development: implications for fertilization failure in humans. Hum Reprod 23:573–580PubMedCrossRefGoogle Scholar
  135. Reinton N, Collas P, Haugen TB, Skalhegg BS, Hansson V, Jahnsen T, Tasken K (2000) Localization of a novel human A-kinase-anchoring protein, hAKAP220, during spermatogenesis. Dev Biol 223:194–204PubMedCrossRefGoogle Scholar
  136. Rivett AJ, Bose S, Brooks P, Broadfoot KI (2001) Regulation of proteasome complexes by gamma-interferon and phosphorylation. Biochimie 83:363–366PubMedCrossRefGoogle Scholar
  137. Rivkin E, Kierszenbaum AL, Gil M, Tres LL (2009) Rnf19a, a ubiquitin protein ligase, and Psmc3, a component of the 26S proteasome, tether to the acrosome membranes and the head-tail coupling apparatus during rat spermatid development. Dev Dyn 238:1851–1861PubMedCrossRefGoogle Scholar
  138. Rodriguez CI, Stewart CL (2007) Disruption of the ubiquitin ligase HERC4 causes defects in spermatozoon maturation and impaired fertility. Dev Biol 312:501–508PubMedCrossRefGoogle Scholar
  139. Rosales O, Opazo C, Diaz ES, Villegas JV, Sanchez R, Morales P (2011) Proteasome activity and proteasome subunit transcripts in human spermatozoa separated by a discontinuous Percoll gradient. Andrologia 43:106–113PubMedCrossRefGoogle Scholar
  140. Rose IA (2005) Ubiquitin at Fox Chase. Proc Natl Acad Sci USA 102:11575–11577PubMedCrossRefGoogle Scholar
  141. Rubin DM, Finley D (1995) Proteolysis. The proteasome: a protein-degrading organelle? Curr Biol 5:854–858PubMedCrossRefGoogle Scholar
  142. Saitoh Y, Sawada H, Yokosawa H (1993) High-molecular-weight protease complexes (proteasomes) of sperm of the ascidian, Halocynthia roretzi: isolation, characterization, and physiological roles in fertilization. Dev Biol 158:238–244PubMedCrossRefGoogle Scholar
  143. Sakai N, Sawada MT, Sawada H (2004) Non-traditional roles of ubiquitin-proteasome system in fertilization and gametogenesis. Int J Biochem Cell Biol 36:776–784PubMedCrossRefGoogle Scholar
  144. Salicioni AM, Platt MD, Wertheimer EV, Arcelay E, Allaire A, Sosnik J, Visconti PE (2007) Signalling pathways involved in sperm capacitation. Soc Reprod Fertil Suppl 65:245–259PubMedGoogle Scholar
  145. Sanchez R, Deppe M, Schulz M, Bravo P, Villegas J, Morales P, Risopatron J (2011) Participation of the sperm proteasome during in vitro fertilisation and the acrosome reaction in cattle. Andrologia 43:114–120PubMedCrossRefGoogle Scholar
  146. Santoro MF, Annand RR, Robertson MM, Peng YW, Brady MJ, Mankovich JA, Hackett MC, Ghayur T, Walter G, Wong WW, Giegel DA (1998) Regulation of protein phosphatase 2A activity by caspase-3 during apoptosis. J Biol Chem 273:13119–13128PubMedCrossRefGoogle Scholar
  147. Sasaki K, Shima H, Kitagawa Y, Irino S, Sugimura T, Nagao M (1990)Identification of members of the protein phosphatase 1 gene family in the rat and enhanced expression of protein phosphatase 1 alpha gene in rat hepatocellular carcinomas. Jpn J Cancer Res 81:1272-1280PubMedCrossRefGoogle Scholar
  148. Sawada H, Yokosawa H, Hoshi M, Ishii S (1983) Ascidian sperm chymotrypsin-like enzyme; participation in fertilization. Experientia 39:377–378PubMedCrossRefGoogle Scholar
  149. Sawada H, Pinto MR, De Santis R (1998) Participation of sperm proteasome in fertilization of the phlebobranch ascidian Ciona intestinalis. Mol Reprod Dev 50:493–498PubMedCrossRefGoogle Scholar
  150. Sawada H, Sakai N, Abe Y, Tanaka E, Takahashi Y, Fujino J, Kodama E, Takizawa S, Yokosawa H (2002) Extracellular ubiquitination and proteasome-mediated degradation of the ascidian sperm receptor. Proc Natl Acad Sci USA 99:1223–1228PubMedCrossRefGoogle Scholar
  151. Shadan S, James PS, Howes EA, Jones R (2004) Cholesterol efflux alters lipid raft stability and distribution during capacitation of boar spermatozoa. Biol Reprod 71:253–265PubMedCrossRefGoogle Scholar
  152. Shao W, Yu Z, Fantus IG, Jin T (2010) Cyclic AMP signaling stimulates proteasome degradation of thioredoxin interacting protein (TxNIP) in pancreatic beta-cells. Cell Signal 22:1240–1246PubMedCrossRefGoogle Scholar
  153. Shi Y (2009) Serine/threonine phosphatases: mechanism through structure. Cell 139:468–484PubMedCrossRefGoogle Scholar
  154. Shima H, Hatano Y, Chun YS, Sugimura T, Zhang Z, Lee EY, Nagao M (1993a) Identification of PP1 catalytic subunit isotypes PP1 gamma 1, PP1 delta and PP1 alpha in various rat tissues. Biochem Biophys Res Commun 192:1289–1296PubMedCrossRefGoogle Scholar
  155. Shima H, Haneji T, Hatano Y, Kasugai I, Sugimura T, Nagao M (1993b) Protein phosphatase 1 gamma 2 is associated with nuclei of meiotic cells in rat testis. Biochem Biophys Res Commun 194:930–937PubMedCrossRefGoogle Scholar
  156. Si Y, Okuno M (1999) Role of tyrosine phosphorylation of flagellar proteins in hamster sperm hyperactivation. Biol Reprod 61:240–246PubMedCrossRefGoogle Scholar
  157. Signorelli J, Diaz ES, Morales P (2011) Human sperm capacitation requires the inhibition of the activity of the serine/threonine phosphatase PP2A. 44th Annual Meeting of the Socitey for the Study of Reproduction, Portlan, Oregon, USAGoogle Scholar
  158. Siva AB, Kameshwari DB, Singh V, Pavani K, Sundaram CS, Rangaraj N, Deenadayal M, Shivaji S (2010) Proteomics-based study on asthenozoospermia: differential expression of proteasome alpha complex. Mol Hum Reprod 16:452–462PubMedCrossRefGoogle Scholar
  159. Smith GD, Wolf DP, Trautman KC, Cruz e Silva EF da, Greengard P, Vijayaraghavan S (1996) Primate sperm contain protein phosphatase 1, a biochemical mediator of motility. Biol Reprod 54:719–727PubMedCrossRefGoogle Scholar
  160. Soler DC, Kadunganattil S, Ramdas S, Myers K, Roca J, Slaughter T, Pilder SH, Vijayaraghavan S (2009) Expression of transgenic PPP1CC2 in the testis of Ppp 1cc-null mice rescues spermatid viability and spermiation but does not restore normal sperm tail ultrastructure, sperm motility, or fertility. Biol Reprod 81:343–352PubMedCrossRefGoogle Scholar
  161. Stoker AW (2005) Protein tyrosine phosphatases and signalling. J Endocrinol 185:19–33PubMedCrossRefGoogle Scholar
  162. Strack S, Kini S, Ebner FF, Wadzinski BE, Colbran RJ (1999) Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain. J Comp Neurol 413:373–384PubMedCrossRefGoogle Scholar
  163. Sumiyoshi E, Sugimoto A, Yamamoto M (2002) Protein phosphatase 4 is required for centrosome maturation in mitosis and sperm meiosis in C. elegans. J Cell Sci 115:1403–1410PubMedGoogle Scholar
  164. Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G (2000) Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Biol Reprod 63:582–590PubMedCrossRefGoogle Scholar
  165. Sutovsky P, Manandhar G, McCauley TC, Caamano JN, Sutovsky M, Thompson WE, Day BN (2004) Proteasomal interference prevents zona pellucida penetration and fertilization in mammals. Biol Reprod 71:1625–1637PubMedCrossRefGoogle Scholar
  166. Suzuki T, Fujinoki M, Shibahara H, Suzuki M (2010) Regulation of hyperactivation by PPP2 in hamster spermatozoa. Reproduction 139:847–856PubMedCrossRefGoogle Scholar
  167. Tanaka K, Chiba T (1998) The proteasome: a protein-destroying machine. Genes Cells 3:499–510PubMedCrossRefGoogle Scholar
  168. Tang FY, Hoskins DD (1975) Phosphoprotein phosphatase of bovine epididymal spermatozoa. Biochem Biophys Res Commun 62:328–335PubMedCrossRefGoogle Scholar
  169. Tapia S, Rojas M, Morales P, Ramirez MA, Diaz ES (2011) The laminin-induced acrosome reaction in human sperm is mediated by Src kinases and the proteasome. Biol Reprod 85:357–366PubMedCrossRefGoogle Scholar
  170. Tash JS, Bracho GE (1994) Regulation of sperm motility: emerging evidence for a major role for protein phosphatases. J Androl 15:505–509PubMedGoogle Scholar
  171. Tash JS, Krinks M, Patel J, Means RL, Klee CB, Means AR (1988) Identification, characterization, and functional correlation of calmodulin-dependent protein phosphatase in sperm. J Cell Biol 106:1625–1633PubMedCrossRefGoogle Scholar
  172. Tipler CP, Hutchon SP, Hendil K, Tanaka K, Fishel S, Mayer RJ (1997) Purification and characterization of 26S proteasomes from human and mouse spermatozoa. Mol Hum Reprod 3:1053–1060PubMedCrossRefGoogle Scholar
  173. Tomes CN, McMaster CR, Saling PM (1996) Activation of mouse sperm phosphatidylinositol-4,5 bisphosphate-phospholipase C by zona pellucida is modulated by tyrosine phosphorylation. Mol Reprod Dev 43:196–204PubMedCrossRefGoogle Scholar
  174. Tonks NK (2006) Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 7:833–846PubMedCrossRefGoogle Scholar
  175. Trockenbacher A, Suckow V, Foerster J, Winter J, Krauss S, Ropers HH, Schneider R, Schweiger S (2001) MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nat Genet 29:287–294PubMedCrossRefGoogle Scholar
  176. Ueki K, Muramatsu T, Kincaid RL (1992) Structure and expression of two isoforms of the murine calmodulin-dependent protein phosphatase regulatory subunit (calcineurin B). Biochem Biophys Res Commun 187:537–543PubMedCrossRefGoogle Scholar
  177. Urner F, Sakkas D (2003) Protein phosphorylation in mammalian spermatozoa. Reproduction 125:17–26PubMedCrossRefGoogle Scholar
  178. Varano G, Lombardi A, Cantini G, Forti G, Baldi E, Luconi M (2008) Src activation triggers capacitation and acrosome reaction but not motility in human spermatozoa. Hum Reprod 23:2652–2662PubMedCrossRefGoogle Scholar
  179. Vijayaraghavan S, Stephens DT, Trautman K, Smith GD, Khatra B, Cruz e Silva EF da, Greengard P (1996) Sperm motility development in the epididymis is associated with decreased glycogen synthase kinase-3 and protein phosphatase 1 activity. Biol Reprod 54:709–718PubMedCrossRefGoogle Scholar
  180. Vijayaraghavan S, Mohan J, Gray H, Khatra B, Carr DW (2000) A role for phosphorylation of glycogen synthase kinase-3alpha in bovine sperm motility regulation. Biol Reprod 62:1647–1654PubMedCrossRefGoogle Scholar
  181. Virshup DM, Shenolikar S (2009) From promiscuity to precision: protein phosphatases get a makeover. Mol Cell 33:537–545PubMedCrossRefGoogle Scholar
  182. Visconti PE (2009) Understanding the molecular basis of sperm capacitation through kinase design. Proc Natl Acad Sci USA 106:667–668PubMedCrossRefGoogle Scholar
  183. Visconti PE, Bailey JL, Moore GD, Pan D, Olds-Clarke P, Kopf GS (1995) Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development 121:1129–1137PubMedGoogle Scholar
  184. Visconti PE, Ning X, Fornes MW, Alvarez JG, Stein P, Connors SA, Kopf GS (1999) Cholesterol efflux-mediated signal transduction in mammalian sperm: cholesterol release signals an increase in protein tyrosine phosphorylation during mouse sperm capacitation. Dev Biol 214:429–443PubMedCrossRefGoogle Scholar
  185. Visconti PE, Krapf D, Vega-Beltran JL de la, Acevedo JJ, Darszon A (2011) Ion channels, phosphorylation and mammalian sperm capacitation. Asian J Androl 13:395–405PubMedCrossRefGoogle Scholar
  186. Wallace RW, Tallant EA, Cheung WY (1980) High levels of a heat-labile calmodulin-binding protein (CaM-BP80) in bovine neostriatum. Biochemistry 19:1831–1837PubMedCrossRefGoogle Scholar
  187. Wennemuth G, Carlson AE, Harper AJ, Babcock DF (2003) Bicarbonate actions on flagellar and Ca2+−channel responses: initial events in sperm activation. Development 130:1317–1326PubMedCrossRefGoogle Scholar
  188. Wojcik C, Benchaib M, Lornage J, Czyba JC, Guerin JF (2000) Proteasomes in human spermatozoa. Int J Androl 23:169–177PubMedCrossRefGoogle Scholar
  189. Wong EY, Tse JY, Yao KM, Tam PC, Yeung WS (2002) VCY2 protein interacts with the HECT domain of ubiquitin-protein ligase E3A. Biochem Biophys Res Commun 296:1104–1111PubMedCrossRefGoogle Scholar
  190. Yamashita K, Yasuda H, Pines J, Yasumoto K, Nishitani H, Ohtsubo M, Hunter T, Sugimura T, Nishimoto T (1990) Okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, activates cdc2/H1 kinase and transiently induces a premature mitosis-like state in BHK21 cells. EMBO J 9:4331–4338PubMedGoogle Scholar
  191. Yanagimachi R (1994) Mammalian fertilization. In: Knobil E, Neill JD (eds) The physiology of reproduction. Raven, New York, pp 189–317Google Scholar
  192. Yeo M, Lin PS, Dahmus ME, Gill GN (2003) A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5. J Biol Chem 278:26078–26085PubMedCrossRefGoogle Scholar
  193. Yi YJ, Manandhar G, Sutovsky M, Li R, Jonakova V, Oko R, Park CS, Prather RS, Sutovsky P (2007) Ubiquitin C-terminal hydrolase-activity is involved in sperm acrosomal function and anti-polyspermy defense during porcine fertilization. Biol Reprod 77:780–793PubMedCrossRefGoogle Scholar
  194. Yokosawa H, Numakunai T, Murao S, Ishii S (1987) Sperm chymotrypsin-like enzymes of different inhibitor-susceptibility as lysins in ascidians. Experientia 43:925–927PubMedCrossRefGoogle Scholar
  195. Yokota N, Sawada H (2007) Sperm proteasomes are responsible for the acrosome reaction and sperm penetration of the vitelline envelope during fertilization of the sea urchin Pseudocentrotus depressus. Dev Biol 308:222–231PubMedCrossRefGoogle Scholar
  196. Zhang F, Hu Y, Huang P, Toleman CA, Paterson AJ, Kudlow JE (2007a) Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. J Biol Chem 282:22460–22471PubMedCrossRefGoogle Scholar
  197. Zhang F, Paterson AJ, Huang P, Wang K, Kudlow JE (2007b) Metabolic control of proteasome function. Physiology 22:373–379PubMedCrossRefGoogle Scholar
  198. Zhang SQ, Yang W, Kontaridis MI, Bivona TG, Wen G, Araki T, Luo J, Thompson JA, Schraven BL, Philips MR, Neel BG (2004) Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol Cell 13:341–355PubMedCrossRefGoogle Scholar
  199. Zhou G, Boomer JS, Tan TH (2004) Protein phosphatase 4 is a positive regulator of hematopoietic progenitor kinase 1. J Biol Chem 279:49551–49561PubMedCrossRefGoogle Scholar
  200. Ziemba H, Bialy LP, Fracki S, Bablok L, Wójcik C (2002) Proteasome localization and ultrastructure of spermatozoa from patients with varicocele. Immunoelectron microscopic study. Folia Histochem Cytobiol 40:169–170PubMedGoogle Scholar
  201. Zimmerman S, Sutovsky P (2009) The sperm proteasome during sperm capacitation and fertilization. J Reprod Immunol 83:19–25PubMedCrossRefGoogle Scholar
  202. Zimmerman SW, Manandhar G, Yi YJ, Gupta SK, Sutovsky M, Odhiambo JF, Powell MD, Miller DJ, Sutovsky P (2011) Sperm proteasomes degrade sperm receptor on the egg zona pellucida during mammalian fertilization. PLoS One 6:e17256PubMedCrossRefGoogle Scholar
  203. Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P (2006) Regulation of murine cardiac 20S proteasomes: role of associating partners. Circ Res 99:372–380PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Janetti Signorelli
    • 1
  • Emilce S. Diaz
    • 1
  • Patricio Morales
    • 1
  1. 1.Biomedical Department, Faculty of Health SciencesUniversity of Antofagasta, Antofagasta, ChileAntofagastaChile

Personalised recommendations