In the past five years, many advances have been made in our understanding of the molecular aspects of GH action. One GH molecule binds to two GH-Rs through two distinct sites on GH, and receptor dimerization is critical for signal transduction. A major subsequent step is the activation of JAK2, which leads to the phosphorylation and activation of several intracellular substrates, including MAP kinases and STATs. The induction of gene transcription by GH can occur through STATs or STAT-like factors, although alternative pathways of gene activation may be mediated by other transcription factors, such as AP-1 and C/EBP. Accessory signal transduction pathways that do not require JAK2 may modulate other biological effects of GH. These pleiomorphic pathways may synergize to produce specific actions of GH.
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