SH2B1 regulation of energy balance, body weight, and glucose metabolism

Figure 2 A model of Src homology 2B1 regulation of leptin signaling. The Src homology 2B1 (SH2B1) homodimers bind to JAK2, IRS1, and/or IRS2. SH2B1-JAK2 interaction increases JAK2 kinase activity, thus globally enhancing leptin signaling. JAK2 phosphorylates STAT3 which subsequently homodimerizes, translocates into the nucleus, and activates its target genes. SH2B1-IRS1/2 interaction allows JAK2 to phosphorylate IRS proteins which subsequently activate the PI 3-kinase pathway. Both the STAT3 and the PI 3-kinase pathways are required for leptin to control energy balance and body weight. JAK2: Janus kinase 2; IRS1: Insulin receptor substrate-1; STAT3: Signal transducer and activator of transcription 3.