Skip to main content
SpringerLink
Log in

Metabolic Effects of Neural and Pancreatic Shp2

  • Chapter
  • First Online:
Protein Tyrosine Phosphatase Control of Metabolism

  • 870 Accesses

Abstract

Shp2, encoded by Ptpn11, is a non-receptor tyrosine phosphatase that contains two Src-homology 2 domains within its structure. Previous biochemical and biological analyses indicate that this enzyme participates in signaling events elicited by various growth factors, cytokines, antigens, and hormones. Recent experiments using the cell type-specific gene knockout approaches in mice have revealed its critical roles in control of metabolism in mammals. In the central nervous system, Shp2 positively transmits leptin signals and may do so by association with the estrogen receptor α, influencing control of food intake, energy expenditure, and body weight. In pancreatic β-cells, Shp2 coordinates multiple pathways to regulate biosynthesis and secretion of insulin in control of glucose homeostasis. Herein we summarize the metabolic functions of Shp2 in the hypothalamus and pancreas.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AAV:

Adeno-associated virus

α-MSH:

Alpha-Melanocyte-stimulating hormone

Akt:

Ak thymoma viral proto-oncogene

BDNF:

Brain-derived neurotrophic factor

CamKIIα:

Ca2+/calmodulin-dependent protein kinase II α

Cbp:

Csk-binding protein

ChIP:

Chromatin immunoprecipitation

Cre:

Cre recombinase

CRE3:

Pan-neuronal cre-transgenic line

Csk:

C-Src tyrosine kinase

Cys:

Cysteine

db/db :

Leptin receptor-deficient mice

E2:

Estradiol-17β

ELISA:

Enzyme-linked immunosorbent assay

ERα:

Estrogen receptor α

Erk:

Extracellular signal-regulated kinase

FoxO1:

Forkhead box protein O1

Glut2:

Glucose transporter 2

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GTP:

Guanosine-5′-triphosphate

HFD:

High-fat diet

Hnf1α:

Hepatocyte nuclear factor 1 alpha

Hnf4α:

Hepatocyte nuclear factor 4 alpha

IGF1:

Insulin-like growth factor 1

Ins1 :

Insulin 1 gene

Ins2 :

Insulin 2 gene

IRS1:

Insulin receptor substrate 1

IRS2:

Insulin receptor substrate 2

Jak2:

Janus kinase 2

LepRb:

Leptin receptor long form

Leu:

Leucine

MAPK:

Mitogen-activated protein kinase

Mek:

Mitogen-activated protein kinase kinase

MODY:

Maturity onset diabetes of the young

NFATc1:

Nuclear factor of activated T cells c1

NIRKO:

Neural-specific insulin receptor knockout

NPY:

Neuropeptide Y

PAG:

Phosphoprotein associated with glycosphingolipid-enriched microdomains

Panc:

Pancreas

PDGF:

Platelet-derived growth factor

Pdx1:

Pancreatic and duodenal homeobox 1

PI3K:

Phosphatidylinositol 3-kinase

PKB:

Protein kinase B

POMC:

Proopiomelanocortin

PTP1B:

Protein tyrosine phosphatase 1B

PTP-1D:

Protein tyrosine phosphatase 1D

PTP-2C:

Protein tyrosine phosphatase 2C

ptpn11:

Protein tyrosine phosphatase non-receptor type 11

PTPs:

Protein tyrosine phosphatases

Raf:

Rapidly accelerated fibrosarcoma

RasGAP:

Ras GTPase activating protein

RT-PCR:

Reverse transcription polymerase chain reaction

RTK:

Receptor tyrosine kinase

SH2:

Src-homology 2

Shp2:

SH2 domain-containing protein tyrosine phosphatase-2

Ser:

Serine

Socs3:

Suppressor of cytokine signaling 3

STAT3:

Signal transducer and activator of transcription 3

Thr:

Threonine

Tyr:

Tyrosine

References

  1. Agazie YM, Hayman MJ (2003) Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling. Mol Cell Biol 23:7875–7886

    Article  PubMed  CAS  Google Scholar 

  2. Ashcroft FM, Rorsman P (2004) Molecular defects in insulin secretion in type-2 diabetes. Rev Endocr Metab Disord 5:135–142

    Article  PubMed  CAS  Google Scholar 

  3. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua SC Jr, Elmquist JK et al (2004) Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42:983–991

    Article  PubMed  CAS  Google Scholar 

  4. Banno R, Zimmer D, De Jonghe BC, Atienza M, Rak K, Yang W, Bence KK (2010) PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice. J Clin Invest 120:720–734

    Article  PubMed  CAS  Google Scholar 

  5. Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, Banks AS, Lavery HJ, Haq AK, Maratos-Flier E et al (2003) STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421:856–859

    Article  PubMed  CAS  Google Scholar 

  6. Binder G (2009) Noonan syndrome, the Ras-MAPK signalling pathway and short stature. Horm Res 71(suppl 2):64–70

    Article  PubMed  CAS  Google Scholar 

  7. Bjornholm M, Munzberg H, Leshan RL, Villanueva EC, Bates SH, Louis GW, Jones JC, Ishida-Takahashi R, Bjorbaek C, Myers MG Jr (2007) Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function. J Clin Invest 117:1354–1360

    Article  PubMed  CAS  Google Scholar 

  8. Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289:2122–2125

    Article  PubMed  CAS  Google Scholar 

  9. Byrne MM, Sturis J, Sobel RJ, Polonsky KS (1996) Elevated plasma glucose 2 h postchallenge predicts defects in beta-cell function. Am J Physiol 270:E572–E579

    PubMed  CAS  Google Scholar 

  10. Carpenter LR, Farruggella TJ, Symes A, Karow ML, Yancopoulos GD, Stahl N (1998) Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor. Proc Natl Acad Sci U S A 95:6061–6066

    Article  PubMed  CAS  Google Scholar 

  11. Carr MC (2003) The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab 88:2404–2411

    Article  PubMed  CAS  Google Scholar 

  12. Case RD, Piccione E, Wolf G, Benett AM, Lechleider RJ, Neel BG, Shoelson SE (1994) SH-PTP2/Syp SH2 domain binding specificity is defined by direct interactions with platelet-derived growth factor beta-receptor, epidermal growth factor receptor, and insulin receptor substrate-1-derived phosphopeptides. J Biol Chem 269:10467–10474

    PubMed  CAS  Google Scholar 

  13. Coll AP, Farooqi IS, Challis BG, Yeo GS, O’Rahilly S (2004) Proopiomelanocortin and energy balance: insights from human and murine genetics. J Clin Endocrinol Metab 89:2557–2562

    Article  PubMed  CAS  Google Scholar 

  14. Dubuc PU (1985) Effects of estrogen on food intake, body weight, and temperature of male and female obese mice. Proc Soc Exp Biol Med 180:468–473

    Article  PubMed  CAS  Google Scholar 

  15. Elbein SC, Hasstedt SJ, Wegner K, Kahn SE (1999) Heritability of pancreatic beta-cell function among nondiabetic members of Caucasian familial type 2 diabetic kindreds. J Clin Endocrinol Metab 84:1398–1403

    Article  PubMed  CAS  Google Scholar 

  16. Fambrough D, McClure K, Kazlauskas A, Lander ES (1999) Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Cell 97:727–741

    Article  PubMed  CAS  Google Scholar 

  17. Feng GS (1999) Shp-2 tyrosine phosphatase: signaling one cell or many. Exp Cell Res 253:47–54

    Article  PubMed  CAS  Google Scholar 

  18. Feng GS, Pawson T (1994) Phosphotyrosine phosphatases with SH2 domains: regulators of signal transduction. Trends Genet 10:54–58

    Article  PubMed  CAS  Google Scholar 

  19. Friedman JM (2004) Modern science versus the stigma of obesity. Nat Med 10:563–569

    Article  PubMed  CAS  Google Scholar 

  20. Gao Q, Horvath TL (2008) Cross-talk between estrogen and leptin signaling in the hypothalamus. Am J Physiol Endocrinol Metab 294:E817–E826

    Article  PubMed  CAS  Google Scholar 

  21. Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL et al (2007) Anorectic estrogen mimics leptin’s effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med 13:89–94

    Article  PubMed  CAS  Google Scholar 

  22. Gao Q, Wolfgang MJ, Neschen S, Morino K, Horvath TL, Shulman GI, Fu XY (2004) Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc Natl Acad Sci U S A 101:4661–4666

    Article  PubMed  CAS  Google Scholar 

  23. Gong Y, Ishida-Takahashi R, Villanueva EC, Fingar DC, Munzberg H, Myers MG Jr (2007) The long form of the leptin receptor regulates STAT5 and ribosomal protein S6 via alternate mechanisms. J Biol Chem 282:31019–31027

    Article  PubMed  CAS  Google Scholar 

  24. Grossmann KS, Rosario M, Birchmeier C, Birchmeier W (2010) The tyrosine phosphatase Shp2 in development and cancer. Adv Cancer Res 106:53–89

    Article  PubMed  CAS  Google Scholar 

  25. Hanafusa H, Torii S, Yasunaga T, Matsumoto K, Nishida E (2004) Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. J Biol Chem 279:22992–22995

    Article  PubMed  CAS  Google Scholar 

  26. He Z, Zhang SS, Meng Q, Li S, Zhu HH, Raquil MA, Alderson N, Zhang H, Wu J, Rui L et al (2012) Shp2 controls female body weight and energy balance by integrating leptin and estrogen signals. Mol Cell Biol 32:1867–1878

    Article  PubMed  CAS  Google Scholar 

  27. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS (2000) Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci U S A 97:12729–12734

    Article  PubMed  CAS  Google Scholar 

  28. Huo L, Gamber K, Greeley S, Silva J, Huntoon N, Leng XH, Bjorbaek C (2009) Leptin-dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab 9:537–547

    Article  PubMed  CAS  Google Scholar 

  29. Jiang L, You J, Yu X, Gonzalez L, Yu Y, Wang Q, Yang G, Li W, Li C, Liu Y (2008) Tyrosine-dependent and -independent actions of leptin receptor in control of energy balance and glucose homeostasis. Proc Natl Acad Sci U S A 105:18619–18624

    Article  PubMed  CAS  Google Scholar 

  30. Jones ME, Thorburn AW, Britt KL, Hewitt KN, Wreford NG, Proietto J, Oz OK, Leury BJ, Robertson KM, Yao S et al (2000) Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci U S A 97:12735–12740

    Article  PubMed  CAS  Google Scholar 

  31. Kazlauskas A, Feng GS, Pawson T, Valius M (1993) The 64-kDa protein that associates with the platelet-derived growth factor receptor beta subunit via Tyr-1009 is the SH2-containing phosphotyrosine phosphatase Syp. Proc Natl Acad Sci U S A 90:6939–6943

    Article  PubMed  CAS  Google Scholar 

  32. Ke Y, Lesperance J, Zhang EE, Bard-Chapeau EA, Oshima RG, Muller WJ, Feng GS (2006) Conditional deletion of Shp2 in the mammary gland leads to impaired lobulo-alveolar outgrowth and attenuated Stat5 activation. J Biol Chem 281:34374–34380

    Article  PubMed  CAS  Google Scholar 

  33. Kernie SG, Liebl DJ, Parada LF (2000) BDNF regulates eating behavior and locomotor activity in mice. EMBO J 19:1290–1300

    Article  PubMed  CAS  Google Scholar 

  34. Krajewska M, Banares S, Zhang EE, Huang X, Scadeng M, Jhala US, Feng GS, Krajewski S (2008) Development of diabesity in mice with neuronal deletion of Shp2 tyrosine phosphatase. Am J Pathol 172:1312–1324

    Article  PubMed  CAS  Google Scholar 

  35. Kuhne MR, Pawson T, Lienhard GE, Feng GS (1993) The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp. J Biol Chem 268: 11479–11481

    PubMed  CAS  Google Scholar 

  36. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR (1999) Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96:329–339

    Article  PubMed  CAS  Google Scholar 

  37. Kulkarni RN, Holzenberger M, Shih DQ, Ozcan U, Stoffel M, Magnuson MA, Kahn CR (2002) beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Nat Genet 31:111–115

    PubMed  CAS  Google Scholar 

  38. Lai LA, Zhao C, Zhang EE, Feng GS (2004) The Shp-2 tyrosine phosphatase. In: Arino J, Alexander D (eds) Protein phosphatases. Springer, Berlin, Heidelberg, pp 275–299

    Chapter  Google Scholar 

  39. Lawrence M, Shao C, Duan L, McGlynn K, Cobb MH (2008) The protein kinases ERK1/2 and their roles in pancreatic beta cells. Acta Physiol (Oxf) 192:11–17

    Article  CAS  Google Scholar 

  40. Lee JY, Muenzberg H, Gavrilova O, Reed JA, Berryman D, Villanueva EC, Louis GW, Leinninger GM, Bertuzzi S, Seeley RJ et al (2008) Loss of cytokine-STAT5 signaling in the CNS and pituitary gland alters energy balance and leads to obesity. PLoS One 3:e1639

    Article  PubMed  Google Scholar 

  41. Li C, Friedman JM (1999) Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc Natl Acad Sci U S A 96:9677–9682

    Article  PubMed  CAS  Google Scholar 

  42. Martens N, Uzan G, Wery M, Hooghe R, Hooghe-Peters EL, Gertler A (2005) Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation. J Biol Chem 280:13817–13823

    Article  PubMed  CAS  Google Scholar 

  43. Matsuo K, Delibegovic M, Matsuo I, Nagata N, Liu S, Bettaieb A, Xi Y, Araki K, Yang W, Kahn BB et al (2010) Altered glucose homeostasis in mice with liver-specific deletion of Src homology phosphatase 2. J Biol Chem 285:39750–39758

    Article  PubMed  CAS  Google Scholar 

  44. Milarski KL, Saltiel AR (1994) Expression of catalytically inactive Syp phosphatase in 3T3 cells blocks stimulation of mitogen-activated protein kinase by insulin. J Biol Chem 269:21239–21243

    PubMed  CAS  Google Scholar 

  45. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, Yoshimura A (2004) Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat Med 10:739–743

    Article  PubMed  CAS  Google Scholar 

  46. Musatov S, Chen W, Pfaff DW, Mobbs CV, Yang XJ, Clegg DJ, Kaplitt MG, Ogawa S (2007) Silencing of estrogen receptor alpha in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. Proc Natl Acad Sci U S A 104:2501–2506

    Article  PubMed  CAS  Google Scholar 

  47. Mutze J, Roth J, Gerstberger R, Hubschle T (2007) Nuclear translocation of the transcription factor STAT5 in the rat brain after systemic leptin administration. Neurosci Lett 417:286–291

    Article  PubMed  Google Scholar 

  48. Nagata N, Matsuo K, Bettaieb A, Bakke J, Matsuo I, Graham J, Xi Y, Liu S, Tomilov A, Tomilova N et al (2012) Hepatic Src homology phosphatase 2 regulates energy balance in mice. Endocrinology 153(7):3158–3169

    Article  PubMed  CAS  Google Scholar 

  49. Nakae J, Biggs WH III, Kitamura T, Cavenee WK, Wright CV, Arden KC, Accili D (2002) Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet 32:245–253

    Article  PubMed  CAS  Google Scholar 

  50. Neel BG, Gu H, Pao L (2003) The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 28:284–293

    Article  PubMed  CAS  Google Scholar 

  51. Noguchi T, Matozaki T, Horita K, Fujioka Y, Kasuga M (1994) Role of SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in insulin-stimulated Ras activation. Mol Cell Biol 14:6674–6682

    PubMed  CAS  Google Scholar 

  52. O’Rahilly S, Barroso I, Wareham NJ (2005) Genetic factors in type 2 diabetes: the end of the beginning? Science 307:370–373

    Article  PubMed  Google Scholar 

  53. Pan Y, Carbe C, Powers A, Feng GS, Zhang X (2010) Sprouty2-modulated Kras signaling rescues Shp2 deficiency during lens and lacrimal gland development. Development 137: 1085–1093

    Article  PubMed  CAS  Google Scholar 

  54. Porter JR, Barrett TG (2005) Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and beta cell failure. J Med Genet 42:893–902

    Article  PubMed  CAS  Google Scholar 

  55. Ren D, Li M, Duan C, Rui L (2005) Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metab 2:95–104

    Article  PubMed  CAS  Google Scholar 

  56. Ren Y, Meng S, Mei L, Zhao ZJ, Jove R, Wu J (2004) Roles of Gab1 and SHP2 in paxillin tyrosine dephosphorylation and Src activation in response to epidermal growth factor. J Biol Chem 279:8497–8505

    Article  PubMed  CAS  Google Scholar 

  57. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R, Lechan RM, Jaenisch R (2001) Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 15:1748–1757

    Article  PubMed  CAS  Google Scholar 

  58. Rogers NH, Perfield JW II, Strissel KJ, Obin MS, Greenberg AS (2009) Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology 150:2161–2168

    Article  PubMed  CAS  Google Scholar 

  59. Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE (2006) Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab 8:538–554

    Article  PubMed  CAS  Google Scholar 

  60. Saxton TM, Henkemeyer M, Gasca S, Shen R, Rossi DJ, Shalaby F, Feng GS, Pawson T (1997) Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine phosphatase Shp-2. EMBO J 16:2352–2364

    Article  PubMed  CAS  Google Scholar 

  61. Sugimoto S, Wandless TJ, Shoelson SE, Neel BG, Walsh CT (1994) Activation of the SH2-containing protein tyrosine phosphatase, SH-PTP2, by phosphotyrosine-containing peptides derived from insulin receptor substrate-1. J Biol Chem 269:13614–13622

    PubMed  CAS  Google Scholar 

  62. Sweet IR, Matschinsky FM (1997) Are there kinetic advantages of GLUT2 in pancreatic glucose sensing? Diabetologia 40:112–119

    Article  PubMed  CAS  Google Scholar 

  63. Tartaglia M, Gelb BD (2005) Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet 6:45–68

    Article  PubMed  CAS  Google Scholar 

  64. Unger RH (1991) Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells. Science 251:1200–1205

    Article  PubMed  CAS  Google Scholar 

  65. Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6:736–742

    Article  PubMed  CAS  Google Scholar 

  66. Yang W, Klaman LD, Chen B, Araki T, Harada H, Thomas SM, George EL, Neel BG (2006) An Shp2/SFK/Ras/Erk signaling pathway controls trophoblast stem cell survival. Dev Cell 10:317–327

    Article  PubMed  CAS  Google Scholar 

  67. You J, Yu Y, Jiang L, Li W, Yu X, Gonzalez L, Yang G, Ke Z, Li C, Liu Y (2010) Signaling through Tyr985 of leptin receptor as an age/diet-dependent switch in the regulation of energy balance. Mol Cell Biol 30:1650–1659

    Article  PubMed  CAS  Google Scholar 

  68. Zhang EE, Chapeau E, Hagihara K, Feng GS (2004) Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism. Proc Natl Acad Sci U S A 101:16064–16069

    Article  PubMed  CAS  Google Scholar 

  69. Zhang SQ, Yang W, Kontaridis MI, Bivona TG, Wen G, Araki T, Luo J, Thompson JA, Schraven BL, Philips MR et al (2004) Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol Cell 13:341–355

    Article  PubMed  Google Scholar 

  70. Zhang SS, Hao E, Yu J, Liu W, Wang J, Levine F, Feng GS (2009) Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic beta-cells. Proc Natl Acad Sci U S A 106:7531–7536

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors thank colleagues for helpful discussion and critical reading of the manuscript and apologize for omitting citation of many other important reports in this short chapter. Work in the Feng laboratory was supported by NIH grants DK073945, DK075916, and HL096125.

Author information

Authors and Affiliations

  1. Department of Pathology and Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093-0864, USA

    Zhao He Ph.D.

  2. School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, China

    Zhao He Ph.D.

  3. Department of Pathology, University of Chicago Medical Center, Chicago, IL, 60637, USA

    Sharon S. Zhang M.D., Ph.D.

  4. Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 200025

    Jianxiu Yu Ph.D.

  5. Department of Pathology, University of California, San Diego, San Diego, CA, 92121, USA

    Gen-Sheng Feng Ph.D.

Authors
  1. Zhao He Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon S. Zhang M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianxiu Yu Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gen-Sheng Feng Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhao He Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Kendra K. Bence

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

He, Z., Zhang, S.S., Yu, J., Feng, GS. (2013). Metabolic Effects of Neural and Pancreatic Shp2. In: Bence, K. (eds) Protein Tyrosine Phosphatase Control of Metabolism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7855-3_9

Download citation

Publish with us

Policies and ethics

Search

Navigation