The molecular basis of growth hormone action.
Recent studies have begun to elucidate the molecular actions of growth hormone, a major regulator of somatic growth and metabolic functions. The cell surface growth hormone receptor, a member of the cytokine receptor superfamily, binds as a dimer to a single growth hormone molecule. Receptor dimerization precedes signal transduction, which is predominantly mediated by the non-receptor tyrosine kinase, Jak2. Activation of Jak2 leads to mitogenic proliferation, phosphorylation of intracellular proteins, MAP kinase activation, activation of Stats 1, 3, and 5, and induction of target gene expression. Specific cytoplasmic domains of the growth hormone receptor mediate Jak2 activation, metabolic actions of growth hormone, Stat activation, and calcium influx.
Thomas
M J
MJ
Department of Internal Medicine, University of Iowa College of Medicine, VA Medical Center, Iowa City 52246, USA. mthomas@icva.gov
D000818:Animals; D002455:Cell Division / Q000502:physiology; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004705:Endocytosis; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000502:physiology; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D053614:Janus Kinase 2; D020935:MAP Kinase Signaling System; D008894:Milk Proteins; D008954:Models, Biological; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051381:Rats; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D019382:Human Growth Hormone; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507927:Jak2 protein, rat; D053614:Janus Kinase 2