JAK2 Phosphorylates IRS in Response to Leptin

Stable Identifier
R-HSA-2671862
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

JAK2 phosphorylates IRS1/2 after IRS1/2 binds SH2B1 in the LEP:LEPR:JAK2:SH2B1 complex (Martin-Romero and Sanchez-Margalet 2001, Li et al. 2007). However, in some cells leptin may only affect phosphorylation of IRS1/2 when insulin signaling subsequently occurs (Szanto and Kahn 2000). As inferred from mouse and rat (Buettner et al. 2008, Hill et al. 2008) phosphorylated IRS1/2 then activates PI3K independently of STAT3 signaling.

Literature References
PubMed ID Title Journal Year
9405487 Divergent signaling capacities of the long and short isoforms of the leptin receptor

Bjørbaek, C, Uotani, S, da Silva, B, Flier, JS

J. Biol. Chem. 1997
10688912 Selective interaction between leptin and insulin signaling pathways in a hepatic cell line

Szanto, I, Kahn, CR

Proc. Natl. Acad. Sci. U.S.A. 2000
11748924 Human leptin activates PI3K and MAPK pathways in human peripheral blood mononuclear cells: possible role of Sam68

Martín-Romero, C, Sánchez-Margalet, V

Cell. Immunol. 2001
17565041 SH2B1 enhances leptin signaling by both Janus kinase 2 Tyr813 phosphorylation-dependent and -independent mechanisms

Li, Z, Zhou, Y, Carter-Su, C, Myers, MG, Rui, L

Mol. Endocrinol. 2007
18382766 Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice

Hill, JW, Williams, KW, Ye, C, Luo, J, Balthasar, N, Coppari, R, Cowley, MA, Cantley, LC, Lowell, BB, Elmquist, JK

J. Clin. Invest. 2008
18516053 Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms

Buettner, C, Buettner, C, Muse, ED, Cheng, A, Chen, L, Scherer, T, Pocai, A, Su, K, Cheng, B, Li, X, Harvey-White, J, Schwartz, GJ, Kunos, G, Rossetti, L

Nat. Med. 2008
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