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Gene Review:

Sh2b1 - SH2B adaptor protein 1

Mus musculus

Synonyms: AI425885, C530001K22Rik, Irip, PSM, Pro-rich, PH and SH2 domain-containing signaling mediator, ...

Ren, D. et al., Duan, C. et al., Iseki, M. et al., Miquet, J.G. et al., Ren, D. et al., et al.

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Disease relevance of Sh2b1

Consequently, SH2-B-/- knockout mice developed age-dependent hyperinsulinemia, hyperglycemia, and glucose intolerance [1].
Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice [2].
SH2-B homozygous null mice were severely hyperphagic and obese and developed a metabolic syndrome characterized by hyperleptinemia, hyperinsulinemia, hyperlipidemia, hepatic steatosis, and hyperglycemia [2].

High impact information on Sh2b1

SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor [3].
APS (adaptor molecule containing PH and SH2 domains) is an intracellular adaptor protein that forms an adaptor family along with Lnk and SH2-B [4].
Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance [1].
Our data suggest that SH2-B is a physiological enhancer of insulin receptor activation and is required for maintaining normal insulin sensitivity and glucose homeostasis during aging [1].
Here we show that SH2-B was expressed in the liver, skeletal muscle, and fat [1].

Biological context of Sh2b1

APS contains a proline-rich region, PH and SH2 domains, and a putative tyrosine phosphorylation site at the C-terminal, and the overall structure resembles those of Lnk and SH2-B [5].
Lnk is an adaptor protein that appears to be involved in signal transduction in lymphocytes, and forms an adaptor protein family with SH2-B [5].
The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains [6].

Anatomical context of Sh2b1

Moreover, overexpression of SH2-B counteracted PTP1B-mediated inhibition of leptin signaling in cultured cells [2].

Associations of Sh2b1 with chemical compounds

Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS [7].
SH2-B is a member of a conserved family of adapter proteins characterized by the presence of a C-terminal SH2 domain, a central pleckstrin homology (PH) domain, and an N-terminal proline rich region [8].

Regulatory relationships of Sh2b1

SH2-B overexpression enhanced mRNA level of PPARgamma in 3T3-L1 cells, whereas PPARgamma levels were reduced in SH2-B-deficient MEFs in response to insulin [9].

Other interactions of Sh2b1

Here we identified SH2-B, a JAK2-interacting protein, as a key regulator of leptin sensitivity, energy balance, and body weight [2].

References

Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. Duan, C., Yang, H., White, M.F., Rui, L. Mol. Cell. Biol. (2004) [Pubmed]
Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Ren, D., Li, M., Duan, C., Rui, L. Cell metabolism. (2005) [Pubmed]
Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Ren, D., Zhou, Y., Morris, D., Li, M., Li, Z., Rui, L. J. Clin. Invest. (2007) [Pubmed]
Increased numbers of B-1 cells and enhanced responses against TI-2 antigen in mice lacking APS, an adaptor molecule containing PH and SH2 domains. Iseki, M., Kubo, C., Kwon, S.M., Yamaguchi, A., Kataoka, Y., Yoshida, N., Takatsu, K., Takaki, S. Mol. Cell. Biol. (2004) [Pubmed]
Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins. Iseki, M., Takaki, S., Takatsu, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling. Li, M., Li, Z., Morris, D.L., Rui, L. Endocrinology (2007) [Pubmed]
Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS. Hu, J., Hubbard, S.R. J. Mol. Biol. (2006) [Pubmed]
Increased SH2-Bbeta content and membrane association in transgenic mice overexpressing GH. Miquet, J.G., Sotelo, A.I., Bartke, A., Turyn, D. J. Endocrinol. (2005) [Pubmed]
Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma messenger ribonucleic acid levels. Yoshiga, D., Sato, N., Torisu, T., Mori, H., Yoshida, R., Nakamura, S., Takaesu, G., Kobayashi, T., Yoshimura, A. Mol. Endocrinol. (2007) [Pubmed]

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