Mechanism of signaling by growth hormone receptor.

Growth hormone (GH) has long been known to stimulate linear growth and regulate metabolism. The cellular mechanism by which GH elicits these effects has only recently begun to be understood. This review provides an overview of a current model of GH signaling. Briefly, binding of GH to GH receptor induces receptor dimerization and activation of the tyrosine kinase JAK2. Tyrosyl phosphorylation of GH receptor and JAK2 recruits and activates signaling molecules such as Stat transcription factors, SHC, and insulin receptor substrates 1 and 2 that lead to the release of second messengers such as diacylglycerol, calcium, and nitric oxide and the activation of enzymes such as mitogen-activated protein kinase, protein kinase C, phospholipase A2, and phosphatidylinositol 3'-kinase. These pathways regulate cellular function including gene transcription, metabolite transport, and enzymatic activity that result in the ability of GH to control body growth and metabolism.