Figure 1.

LepRb signaling events. A. In wild type (WT) mice (A), leptin binding activates the LepRb-associated janus associated kinase 2 (Jak2), a tyrosine kinase that mediates tyrosine phosphorylation of LepRb to promote several intracellular signaling events: 1) LepRb Tyr⁹⁸⁵ recruits SH2-containing tyrosine phosphatase (SHP-2) and growth factor binding 2 (GRB2) and to promote the activation of extracellular regulated kinases 1 and 2 (ERK1/2). ERK1/2 phosphorylates downstream targets and induces the transcription of genes. 2) Phosphorylated Tyr1107 binds and mediates the phosphorylation-dependent activation of STAT5 and 3) Tyr1138 recruits STAT3, which promotes the transcription many different genes. In l/l mice (B), substitution of LepRb Tyr⁹⁸⁵ with LepRb L⁹⁸⁵ prevents leptin mediated ERK 1/2 activation in AMs from l/l mice. AMs obtained from WT and l/l mice were cultured with media alone or with exogenous leptin (50 ng/ml) for 30 min and evaluated for pERK1/2 and total ERK 1/2 by immunoblot analysis. Protein levels were determined by densitometric analysis of immunoblots from 5 separate experiments (B).*, P<0.001 vs untreated WT using the students t-test.