Session: S04-GH at the Cutting Edge
Room 303 (Moscone Center)
Among its diverse actions on cells, GH regulates the actin cytoskeleton, enhancing membrane ruffling and cell migration. SH2B1, a scaffolding protein and JAK2 binding protein, has recently been identified as a human obesity gene. Patients with point mutations in SH2B1 exhibit severe childhood obesity, insulin resistance and in some cases, maladaptive behavior. Accumulation of macrophages in tissues such as adipose tissue is a central feature of the inflammatory response to obesity, a response that contributes to insulin resistance. Consistent with GH regulating the actin cytoskeleton and cell motility, we recently showed that GH promotes chemotactic migration of macrophages. Chemoattraction is an essential step for immune cells, including macrophages, to infiltrate host tissues and respond to infection. In this presentation, we will discuss the mechanism by which SH2B1 contributes to GH-dependent cell motility, the mechanism by which phosphorylation affects the ability of SH2B1 to regulate cell motility, and the impact of obesity-related human mutations in SH2B1 on GH-dependent cell motility.