G-Protein-Coupled Receptor-Signaling Components in Membrane Raft and Caveolae Microdomains

  • H. H. Patel
  • F. Murray
  • P. A. Insel
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 186)


The efficiency of signal transduction in cells derives in part from subcellular, in particular plasma membrane, microdomains that organize signaling molecules and signaling complexes. Two related plasma membrane domains that compartmentalize G-protein coupled receptor (GPCR) signaling complexes are lipid (membrane) rafts, domains that are enriched in certain lipids, including cholesterol and sphingolipids, and caveolae, a subset of lipid rafts that are enriched in the protein caveolin. This review focuses on the properties of lipid rafts and caveolae, the mechanisms by which they localize signaling molecules and the identity of GPCR signaling components that are organized in these domains.


Lipid Raft Adenylyl Cyclase Membrane Raft Pulmonary Artery Smooth Muscle Cell Caveolin Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abrahamsen H, Baillie G, Ngai J et al (2004) TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. J Immunol 173:4847–4858PubMedGoogle Scholar
  2. Baillie GS, Scott JD, Houslay MD (2005) Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract. FEBS Lett 579:3264–3270PubMedCrossRefGoogle Scholar
  3. Ballard-Croft C, Locklar AC, Kristo G et al (2006) Regional myocardial ischemia-induced activation of MAPKs is associated with subcellular redistribution of caveolin and cholesterol. Am J Physiol Heart Circ Physiol 291:H658–H667PubMedCrossRefGoogle Scholar
  4. Banfi C, Brioschi M, Wait R et al (2006) Proteomic analysis of membrane microdomains derived from both failing and non-failing human hearts. Proteomics 6:1976–1988PubMedCrossRefGoogle Scholar
  5. Becher A, McIlhinney RA (2005) Consequences of lipid raft association on G-protein-coupled receptor function. Biochem Soc Symp 72:151–164PubMedGoogle Scholar
  6. Berditchevski F, Odintsova E (2007) Tetraspanins as regulators of protein trafficking. Traffic 8:89–96PubMedCrossRefGoogle Scholar
  7. Bergman RN, Hechter O (1978) Neurohypophyseal hormone-responsive renal adenylate cyclase. IV. A random-hit matrix model for coupline in a hormone-sensitive adenylate cyclase system. J Biol Chem 253:3238–3250PubMedGoogle Scholar
  8. Bhatnagar A, Sheffler DJ, Kroeze WK et al (2004) Caveolin-1 interacts with 5-HT2A serotonin receptors and profoundly modulates the signaling of selected Galphaq-coupled protein receptors. J Biol Chem 279:34614–34623PubMedCrossRefGoogle Scholar
  9. Boyd NL, Park H, Yi H et al (2003) Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells. Am J Physiol Heart Circ Physiol 285:H1113–H1122PubMedGoogle Scholar
  10. Carver LA, Schnitzer JE (2003) Caveolae: mining little caves for new cancer targets. Nat Rev Cancer 3:571–581PubMedCrossRefGoogle Scholar
  11. Cavallo-Medved D, Mai J, Dosescu J et al (2005) Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells. J Cell Sci 118:1493–1503PubMedCrossRefGoogle Scholar
  12. Chini B, Parenti M (2004) G-protein coupled receptors in lipid rafts and caveolae: how, when and why do they go there? J Mol Endocrinol 32:325–338PubMedCrossRefGoogle Scholar
  13. Cho KA, Ryu SJ, Park JS et al (2003) Senescent phenotype can be reversed by reduction of caveolin status. J Biol Chem 278:27789–27795PubMedCrossRefGoogle Scholar
  14. Cohen AW, Park DS, Woodman SE et al (2003a) Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. Am J Physiol Cell Physiol 284:C457–C474PubMedGoogle Scholar
  15. Cohen AW, Razani B, Wang XB et al (2003b) Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. Am J Physiol Cell Physiol 285:C222–C235PubMedGoogle Scholar
  16. Cohen AW, Hnasko R, Schubert W et al (2004) Role of caveolae and caveolins in health and disease. Physiol Rev 84:1341–1379PubMedCrossRefGoogle Scholar
  17. Couet J, Li S, Okamoto T et al (1997a) Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J Biol Chem 272:6525–6533PubMedCrossRefGoogle Scholar
  18. Couet J, Sargiacomo M, Lisanti MP (1997b) Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 272:30429–30438PubMedCrossRefGoogle Scholar
  19. Crossthwaite AJ, Seebacher T, Masada N et al (2005) The cytosolic domains of Ca2+-sensitive adenylyl cyclases dictate their targeting to plasma membrane lipid rafts. J Biol Chem 280:6380–6391PubMedCrossRefGoogle Scholar
  20. Del Pozo MA, Schwartz MA (2007) Rac, membrane heterogeneity, caveolin and regulation of growth by integrins. Trends Cell Biol 17:246–250PubMedCrossRefGoogle Scholar
  21. Durr E, Yu J, Krasinska KM et al (2004) Direct proteomic mapping of the lung microvascular endothelial cell surface in vivo and in cell culture. Nat Biotechnol 22:985–992PubMedCrossRefGoogle Scholar
  22. Echarri A, Del Pozo MA (2006) Caveolae internalization regulates integrin-dependent signaling pathways. Cell Cycle 5:2179–2182PubMedGoogle Scholar
  23. Engelman JA, Chu C, Lin A et al (1998) Caveolin-mediated regulation of signaling along the p42/44 MAP kinase cascade in vivo. A role for the caveolin-scaffolding domain. FEBS Lett 428:205–211PubMedCrossRefGoogle Scholar
  24. Feron O, Balligand JL (2006) Caveolins and the regulation of endothelial nitric oxide synthase in the heart. Cardiovasc Res 69:788–797PubMedCrossRefGoogle Scholar
  25. Feron O, Dessy C, Opel DJ et al (1998) Modulation of the endothelial nitric-oxide synthase-caveolin interaction in cardiac myocytes. Implications for the autonomic regulation of heart rate. J Biol Chem 273:30249–30254PubMedCrossRefGoogle Scholar
  26. Fischmeister R (2006) Is cAMP good or bad?: Depends on where it’s made. Circ Res 98:582–584PubMedCrossRefGoogle Scholar
  27. Foster LJ, De Hoog CL, Mann M (2003) Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors. Proc Natl Acad Sci USA 100:5813–5818PubMedCrossRefGoogle Scholar
  28. Fox TE, Houck KL, O’Neill SM et al (2007) Ceramide recruits and activates protein kinase C zeta (PKC zeta) within structured membrane microdomains. J Biol Chem 282:12450–12457PubMedCrossRefGoogle Scholar
  29. Galbiati F, Volonte D, Engelman JA et al (1998) Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade. EMBO J 17:6633–6648PubMedCrossRefGoogle Scholar
  30. Garcia-Cardena G, Martasek P, Masters BS et al (1997) Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J Biol Chem 272:25437–25440PubMedCrossRefGoogle Scholar
  31. Gosens R, Stelmack GL, Dueck G et al (2006) Role of caveolin-1 in p42/p44 MAP kinase activation and proliferation of human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 291:L523–L534PubMedCrossRefGoogle Scholar
  32. Gratton JP, Bernatchez P, Sessa WC (2004) Caveolae and caveolins in the cardiovascular system. Circ Res 94:1408–1417PubMedCrossRefGoogle Scholar
  33. Ha H, Pak Y (2005) Modulation of the caveolin-3 and Akt status in caveolae by insulin resistance in H9c2 cardiomyoblasts. Exp Mol Med 37:169–178PubMedGoogle Scholar
  34. Head BP, Insel PA (2007) Do caveolins regulate cells by actions outside of caveolae? Trends Cell Biol 17:51–57PubMedCrossRefGoogle Scholar
  35. Head BP, Patel HH, Roth DM et al (2005) G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. J Biol Chem 280:31036–31044PubMedCrossRefGoogle Scholar
  36. Head BP, Patel HH, Roth DM et al (2006) Microtubules and actin microfilaments regulate lipid raft/caveolae localization of adenylyl cyclase signaling components. J Biol Chem 281:26391–26399PubMedCrossRefGoogle Scholar
  37. Heijnen HF, Waaijenborg S, Crapo JD et al (2004) Colocalization of eNOS and the catalytic subunit of PKA in endothelial cell junctions: a clue for regulated NO production. J Histochem Cytochem 52:1277–1285PubMedCrossRefGoogle Scholar
  38. Helms JB, Zurzolo C (2004) Lipids as targeting signals: lipid rafts and intracellular trafficking. Traffic 5:247–254PubMedCrossRefGoogle Scholar
  39. Hill MM, Bastiani M, Luetterforst R et al (2008) PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 132:113–124PubMedCrossRefGoogle Scholar
  40. Houslay MD, Baillie GS, Maurice DH (2007) cAMP-Specific phosphodiesterase-4 enzymes in the cardiovascular system: a molecular toolbox for generating compartmentalized cAMP signaling. Circ Res 100:950–966PubMedCrossRefGoogle Scholar
  41. Huang CS, Zhou J, Feng AK et al (1999) Nerve growth factor signaling in caveolae-like domains at the plasma membrane. J Biol Chem 274:36707–36714PubMedCrossRefGoogle Scholar
  42. Iiri T, Backlund PS Jr, Jones TL et al (1996) Reciprocal regulation of Gs alpha by palmitate and the beta gamma subunit. Proc Natl Acad Sci USA 93:14592–14597PubMedCrossRefGoogle Scholar
  43. Insel PA, Patel HH (2007) Do studies in caveolin-knockouts teach us about physiology and pharmacology or instead, the ways mice compensate for ‘lost proteins’? Br J Pharmacol 150:251–254PubMedCrossRefGoogle Scholar
  44. Insel PA, Head BP, Patel HH et al (2005) Compartmentation of G-protein-coupled receptors and their signalling components in lipid rafts and caveolae. Biochem Soc Trans 33:1131–1134PubMedCrossRefGoogle Scholar
  45. Jacobson K, Mouritsen OG, Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9:7–14PubMedCrossRefGoogle Scholar
  46. Kim HP, Wang X, Nakao A et al (2005) Caveolin-1 expression by means of p38beta mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide. Proc Natl Acad Sci USA 102:11319–11324PubMedCrossRefGoogle Scholar
  47. Kim HA, Kim KH, Lee RA (2006) Expression of caveolin-1 is correlated with Akt-1 in colorectal cancer tissues. Exp Mol Pathol 80:165–170PubMedCrossRefGoogle Scholar
  48. Krajewska WM, Maslowska I (2004) Caveolins: structure and function in signal transduction. Cell Mol Biol Lett 9:195–220PubMedGoogle Scholar
  49. Kurzchalia TV, Dupree P, Parton RG et al (1992) VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles. J Cell Biol 118:1003–1014PubMedCrossRefGoogle Scholar
  50. Lee H, Volonte D, Galbiati F et al (2000) Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette. Mol Endocrinol 14:1750–1775PubMedCrossRefGoogle Scholar
  51. Lee H, Woodman SE, Engelman JA et al (2001) Palmitoylation of caveolin-1 at a single site (Cys-156) controls its coupling to the c-Src tyrosine kinase: targeting of dually acylated molecules (GPI-linked, transmembrane, or cytoplasmic) to caveolae effectively uncouples c-Src and caveolin-1 (TYR-14). J Biol Chem 276:35150–35158PubMedCrossRefGoogle Scholar
  52. Lefkowitz RJ, Shenoy SK (2005) Transduction of receptor signals by beta-arrestins. Science 308:512–517PubMedCrossRefGoogle Scholar
  53. Levin AM, Murase K, Jackson PJ et al (2007) Double barrel shotgun scanning of the caveolin-1 scaffolding domain. ACS Chem Biol 2:493–500PubMedCrossRefGoogle Scholar
  54. Li S, Okamoto T, Chun M et al (1995) Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. J Biol Chem 270:15693–15701PubMedCrossRefGoogle Scholar
  55. Li S, Couet J, Lisanti MP (1996a) Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 271:29182–29190PubMedCrossRefGoogle Scholar
  56. Li S, Seitz R, Lisanti MP (1996b) Phosphorylation of caveolin by src tyrosine kinases. The alpha-isoform of caveolin is selectively phosphorylated by v-Src in vivo. J Biol Chem 271:3863–3868PubMedCrossRefGoogle Scholar
  57. Li L, Ren CH, Tahir SA et al (2003) Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Mol Cell Biol 23:9389–9404PubMedCrossRefGoogle Scholar
  58. Liu L, Pilch PF (2008) A critical role of cavin (polymerase I and transcript release factor) in caveolae formation and organization. J Biol Chem 283:4314–4322PubMedCrossRefGoogle Scholar
  59. Liu P, Rudick M, Anderson RG (2002) Multiple functions of caveolin-1. J Biol Chem 277:41295–41298PubMedCrossRefGoogle Scholar
  60. Lucero HA, Robbins PW (2004) Lipid rafts-protein association and the regulation of protein activity. Arch Biochem Biophys 426:208–224PubMedCrossRefGoogle Scholar
  61. Luttrell LM, Lefkowitz RJ (2002) The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115:455–465PubMedGoogle Scholar
  62. Lynch MJ, Hill EV, Houslay MD (2006) Intracellular targeting of phosphodiesterase-4 underpins compartmentalized cAMP signaling. Curr Top Dev Biol 75:225–259PubMedCrossRefGoogle Scholar
  63. Malbon CC, Tao J, Shumay E et al (2004) AKAP (A-kinase anchoring protein) domains: beads of structure-function on the necklace of G-protein signalling. Biochem Soc Trans 32:861–864PubMedCrossRefGoogle Scholar
  64. Marguet D, Lenne PF, Rigneault H et al (2006) Dynamics in the plasma membrane: how to combine fluidity and order. EMBO J 25:3446–3457PubMedCrossRefGoogle Scholar
  65. McMahon KA, Zhu M, Kwon SW et al (2006) Detergent-free caveolae proteome suggests an interaction with ER and mitochondria. Proteomics 6:143–152PubMedCrossRefGoogle Scholar
  66. McPhee I, Yarwood SJ, Scotland G et al (1999) Association with the SRC family tyrosyl kinase LYN triggers a conformational change in the catalytic region of human cAMP-specific phosphodiesterase HSPDE4A4B. Consequences for rolipram inhibition. J Biol Chem 274:11796–11810PubMedCrossRefGoogle Scholar
  67. Morris R, Cox H, Mombelli E et al (2004) Rafts, little caves and large potholes: how lipid structure interacts with membrane proteins to create functionally diverse membrane environments. Subcell Biochem 37:35–118PubMedGoogle Scholar
  68. Munro S (2003) Lipid rafts: elusive or illusive? Cell 115:377–388PubMedCrossRefGoogle Scholar
  69. Murray F, Patel H, Suda R et al (2006) Caveolar localization and caveolin-1 regulation of PDE5 in human pulmonary artery smooth muscle cells. FASEB J. 20:A543Google Scholar
  70. Murthy KS, Makhlouf GM (2000) Heterologous desensitization mediated by G protein-specific binding to caveolin. J Biol Chem 275:30211–30219PubMedCrossRefGoogle Scholar
  71. Nichols B (2003) Caveosomes and endocytosis of lipid rafts. J Cell Sci 116:4707–4714PubMedCrossRefGoogle Scholar
  72. Nilsson R, Ahmad F, Sward K et al (2006) Plasma membrane cyclic nucleotide phosphodiesterase 3B (PDE3B) is associated with caveolae in primary adipocytes. Cell Signal 18:1713–1721PubMedCrossRefGoogle Scholar
  73. Oh P, Schnitzer JE (2001) Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default. Mol Biol Cell 12:685–698PubMedGoogle Scholar
  74. Okamoto T, Schlegel A, Scherer PE et al (1998) Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J Biol Chem 273:5419–5422PubMedCrossRefGoogle Scholar
  75. Ono K, Iwanaga Y, Hirayama M et al (2004) Contribution of caveolin-1 alpha and Akt to TNF-alpha-induced cell death. Am J Physiol Lung Cell Mol Physiol 287:L201–L209PubMedCrossRefGoogle Scholar
  76. Oshikawa J, Otsu K, Toya Y et al (2004) Insulin resistance in skeletal muscles of caveolin-3-null mice. Proc Natl Acad Sci USA 101:12670–12675PubMedCrossRefGoogle Scholar
  77. Ostrom RS, Insel PA (2004) The evolving role of lipid rafts and caveolae in G protein-coupled receptor signaling: implications for molecular pharmacology. Br J Pharmacol 143:235–245PubMedCrossRefGoogle Scholar
  78. Ostrom RS, Insel PA (2006) Methods for the study of signaling molecules in membrane lipid rafts and caveolae. Methods Mol Biol 332:181–191PubMedGoogle Scholar
  79. Ostrom RS, Post SR, Insel PA (2000) Stoichiometry and compartmentation in G protein-coupled receptor signaling: implications for therapeutic interventions involving G(s). J Pharmacol Exp Ther 294:407–412PubMedGoogle Scholar
  80. Ostrom RS, Gregorian C, Drenan RM et al (2001) Receptor number and caveolar co-localization determine receptor coupling efficiency to adenylyl cyclase. J Biol Chem 276:42063–42069PubMedCrossRefGoogle Scholar
  81. Ostrom RS, Bundey RA, Insel PA (2004) Nitric oxide inhibition of adenylyl cyclase type 6 activity is dependent upon lipid rafts and caveolin signaling complexes. J Biol Chem 279:19846–19853PubMedCrossRefGoogle Scholar
  82. Palade G (1953) Fine structure of blood capilaries. J Appl Physiol 24:1424–1436Google Scholar
  83. Parat MO, Fox PL (2001) Palmitoylation of caveolin-1 in endothelial cells is post-translational but irreversible. J Biol Chem 276:15776–15782PubMedCrossRefGoogle Scholar
  84. Park SC, Cho KA, Jang IS et al (2004) Functional efficiency of the senescent cells: replace or restore? Ann N Y Acad Sci 1019:309–316PubMedCrossRefGoogle Scholar
  85. Parton RG, Simons K (2007) The multiple faces of caveolae. Nat Rev Mol Cell Biol 8:185–194PubMedCrossRefGoogle Scholar
  86. Patel HH, Tsutsumi YM, Head BP et al (2007a) Mechanisms of cardiac protection from ischemia/reperfusion injury: a role for caveolae and caveolin-1. FASEB J 21:1565–1574PubMedCrossRefGoogle Scholar
  87. Patel HH, Zhang S, Murray F et al (2007b) Increased smooth muscle cell expression of caveolin-1 and caveolae contribute to the pathophysiology of idiopathic pulmonary arterial hypertension. FASEB J 21:2970–2979PubMedCrossRefGoogle Scholar
  88. Peart JN, Headrick JP (2007) Adenosinergic cardioprotection: multiple receptors, multiple pathways. Pharmacol Ther 114:208–221PubMedCrossRefGoogle Scholar
  89. Pike LJ (2003) Lipid rafts: bringing order to chaos. J Lipid Res 44:655–667PubMedCrossRefGoogle Scholar
  90. Pike LJ (2004) Lipid rafts: heterogeneity on the high seas. Biochem J 378:281–292PubMedCrossRefGoogle Scholar
  91. Pike LJ (2005) Growth factor receptors, lipid rafts and caveolae: an evolving story. Biochim Biophys Acta 1746:260–273PubMedCrossRefGoogle Scholar
  92. Pike LJ (2006) Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function. J Lipid Res 47:1597–1598PubMedCrossRefGoogle Scholar
  93. Prevostel C, Alice V, Joubert D et al (2000) Protein kinase C(alpha) actively downregulates through caveolae-dependent traffic to an endosomal compartment. J Cell Sci 113(Pt 14):2575–2584PubMedGoogle Scholar
  94. Prior IA, Harding A, Yan J et al (2001) GTP-dependent segregation of H-ras from lipid rafts is required for biological activity. Nat Cell Biol 3:368–375PubMedCrossRefGoogle Scholar
  95. Ratajczak P, Damy T, Heymes C et al (2003) Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat. Cardiovasc Res 57:358–369PubMedCrossRefGoogle Scholar
  96. Razani B, Lisanti MP (2001) Two distinct caveolin-1 domains mediate the functional interaction of caveolin-1 with protein kinase A. Am J Physiol Cell Physiol 281:C1241–C1250PubMedGoogle Scholar
  97. Razani B, Rubin CS, Lisanti MP (1999) Regulation of cAMP-mediated signal transduction via interaction of caveolins with the catalytic subunit of protein kinase A. J Biol Chem 274:26353–26360PubMedCrossRefGoogle Scholar
  98. Razani B, Engelman JA, Wang XB et al (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276:38121–38138PubMedCrossRefGoogle Scholar
  99. Razzaq TM, Ozegbe P, Jury EC et al (2004) Regulation of T-cell receptor signalling by membrane microdomains. Immunology 113:413–426PubMedCrossRefGoogle Scholar
  100. Renner U, Glebov K, Lang T et al (2007) Localization of the mouse 5-hydroxytryptamine(1A) receptor in lipid microdomains depends on its palmitoylation and is involved in receptor-mediated signaling. Mol Pharmacol 72:502–513PubMedCrossRefGoogle Scholar
  101. Resh MD (2006) Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci STKE 2006:re14PubMedCrossRefGoogle Scholar
  102. Rodgers W, Farris D, Mishra S (2005) Merging complexes: properties of membrane raft assembly during lymphocyte signaling. Trends Immunol 26:97–103PubMedCrossRefGoogle Scholar
  103. Rothberg KG, Heuser JE, Donzell WC et al (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682PubMedCrossRefGoogle Scholar
  104. Roy S, Plowman S, Rotblat B et al (2005) Individual palmitoyl residues serve distinct roles in H-ras trafficking, microlocalization, and signaling. Mol Cell Biol 25:6722–6733PubMedCrossRefGoogle Scholar
  105. Rybin VO, Xu X, Steinberg SF (1999) Activated protein kinase C isoforms target to cardiomyocyte caveolae: stimulation of local protein phosphorylation. Circ Res 84:980–988PubMedGoogle Scholar
  106. Sampson LJ, Hayabuchi Y, Standen NB et al (2004) Caveolae localize protein kinase A signaling to arterial ATP-sensitive potassium channels. Circ Res 95:1012–1018PubMedCrossRefGoogle Scholar
  107. Sbaa E, Frerart F, Feron O (2005) The double regulation of endothelial nitric oxide synthase by caveolae and caveolin: a paradox solved through the study of angiogenesis. Trends Cardiovasc Med 15:157–162PubMedCrossRefGoogle Scholar
  108. Schutzer WE, Reed JF, Mader SL (2005) Decline in caveolin-1 expression and scaffolding of G protein receptor kinase-2 with age in Fischer 344 aortic vascular smooth muscle. Am J Physiol Heart Circ Physiol 288:H2457–H2464PubMedCrossRefGoogle Scholar
  109. Sedding DG, Hermsen J, Seay U et al (2005) Caveolin-1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro and in vivo. Circ Res 96:635–642PubMedCrossRefGoogle Scholar
  110. Shack S, Wang XT, Kokkonen GC et al (2003) Caveolin-induced activation of the phosphatidylinositol 3-kinase/Akt pathway increases arsenite cytotoxicity. Mol Cell Biol 23:2407–2414PubMedCrossRefGoogle Scholar
  111. Simons K, Ehehalt R (2002) Cholesterol, lipid rafts, and disease. J Clin Invest 110:597–603PubMedGoogle Scholar
  112. Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175:720–731PubMedCrossRefGoogle Scholar
  113. Smythe GM, Rando TA (2006) Altered caveolin-3 expression disrupts PI(3) kinase signaling leading to death of cultured muscle cells. Exp Cell Res 312:2816–2825PubMedCrossRefGoogle Scholar
  114. Smythe GM, Eby JC, Disatnik MH et al (2003) A caveolin-3 mutant that causes limb girdle muscular dystrophy type 1C disrupts Src localization and activity and induces apoptosis in skeletal myotubes. J Cell Sci 116:4739–4749PubMedCrossRefGoogle Scholar
  115. Song KS, Li S, Okamoto T et al (1996) Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains. J Biol Chem 271:9690–9697PubMedCrossRefGoogle Scholar
  116. Song KS, Sargiacomo M, Galbiati F et al (1997) Targeting of a G alpha subunit (Gi1 alpha) and c-Src tyrosine kinase to caveolae membranes: clarifying the role of N-myristoylation. Cell Mol Biol 43:293–303PubMedGoogle Scholar
  117. Sonveaux P, Martinive P, DeWever J et al (2004) Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. Circ Res 95:154–161PubMedCrossRefGoogle Scholar
  118. Sprenger RR, Horrevoets AJ (2007) Proteomic study of caveolae and rafts isolated from human endothelial cells. Methods Mol Biol 357:199–213PubMedGoogle Scholar
  119. Swaney JS, Patel HH, Yokoyama U et al (2006) Focal adhesions in (myo) fibroblasts scaffold adenylyl cyclase with phosphorylated caveolin. J Biol Chem 281:17173–17179PubMedCrossRefGoogle Scholar
  120. Toya Y, Schwencke C, Couet J et al (1998) Inhibition of adenylyl cyclase by caveolin peptides. Endocrinology 139:2025–2031PubMedCrossRefGoogle Scholar
  121. van Deurs B, Roepstorff K, Hommelgaard AM et al (2003) Caveolae: anchored, multifunctional platforms in the lipid ocean. Trends Cell Biol 13:92–100PubMedCrossRefGoogle Scholar
  122. Venema VJ, Ju H, Zou R et al (1997) Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain. J Biol Chem 272:28187–28190PubMedCrossRefGoogle Scholar
  123. Volonte D, Galbiati F, Pestell RG et al (2001) Cellular stress induces the tyrosine phosphorylation of caveolin-1 (Tyr(14)) via activation of p38 mitogen-activated protein kinase and c-Src kinase. Evidence for caveolae, the actin cytoskeleton, and focal adhesions as mechanical sensors of osmotic stress. J Biol Chem 276:8094–8103PubMedCrossRefGoogle Scholar
  124. von Zastrow M (2003) Mechanisms regulating membrane trafficking of G protein-coupled receptors in the endocytic pathway. Life Sci 74:217–224CrossRefGoogle Scholar
  125. Wang XM, Zhang Y, Kim HP et al (2006) Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med 203:2895–2906PubMedCrossRefGoogle Scholar
  126. Willoughby D, Cooper DM (2007) Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains. Physiol Rev 87:965–1010PubMedCrossRefGoogle Scholar
  127. Woodman SE, Park DS, Cohen AW et al (2002) Caveolin-3 knock-out mice develop a progressive cardiomyopathy and show hyperactivation of the p42/44 MAPK cascade. J Biol Chem 277:38988–38997PubMedCrossRefGoogle Scholar
  128. Wyse BD, Prior IA, Qian H et al (2003) Caveolin interacts with the angiotensin II type 1 receptor during exocytic transport but not at the plasma membrane. J Biol Chem 278:23738–23746PubMedCrossRefGoogle Scholar
  129. Yamabhai M, Anderson RG (2002) Second cysteine-rich region of epidermal growth factor receptor contains targeting information for caveolae/rafts. J Biol Chem 277:24843–24846PubMedCrossRefGoogle Scholar
  130. Yamada E (1955) The fine structure of the gall bladder epithelium of the mouse. J Biophys Biochem Cytol 1:445–458PubMedCrossRefGoogle Scholar
  131. Yamamoto M, Okumura S, Oka N et al (1999) Downregulation of caveolin expression by cAMP signal. Life Sci 64:1349–1357PubMedCrossRefGoogle Scholar
  132. Younes A, Lyashkov AE, Graham D et al (2008) Ca 2+-stimulated basal adenylyl cyclase activity localization in membrane lipid microdomains of cardiac sinoatrial nodal pacemaker cells. J Biol Chem [ePub ahead of print 10.1074/jbc.M707540200]Google Scholar
  133. Zhang B, Peng F, Wu D et al (2007) Caveolin-1 phosphorylation is required for stretch-induced EGFR and Akt activation in mesangial cells. Cell Signal 19:1690–1700PubMedCrossRefGoogle Scholar
  134. Zhao H, Loh HH, Law PY (2006) Adenylyl cyclase superactivation induced by long-term treatment with opioid agonist is dependent on receptor localized within lipid rafts and is independent of receptor internalization. Mol Pharmacol 69:1421–1432PubMedCrossRefGoogle Scholar
  135. Zhuang L, Lin J, Lu ML et al (2002) Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer cells. Cancer Res 62:2227–2231PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • H. H. Patel
    • 1
  • F. Murray
    • 2
  • P. A. Insel
    • 3
  1. 1.Departments of AnesthesiologyUniversity of California, San DiegoLa JollaUSA
  2. 2.PharmacologyUniversity of California, San DiegoLa JollaUSA
  3. 3.Department of PharmacologyUniversity of California, San DiegoLa JollaUSA

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