The role of STAT proteins in growth hormone signaling.
Growth hormone (GH) has long been known to be the body's primary regulator of body growth and a regulator of metabolism, yet the mechanisms by which GH regulates the transcription of specific genes required for these processes are just now being delineated. GH binding to its receptor recruits and activates the receptor-associated JAK2 that in turn phosphorylates tyrosines within itself and the GH receptor. These tyrosines form binding sites for a number of signaling proteins, including members of the family of signal transducers and activators of transcription (STAT). Among the known signaling molecules for GH, STAT proteins play a particularly prominent role in the regulation of gene transcription. This paper will review what is currently understood about which STAT proteins are regulated by GH, how they are regulated by GH, the GH-dependent genes they regulate, and discuss current theories about how GH-activated STAT signaling is regulated. Particular attention will be given to the novel role that STAT5 plays in sexually dimorphic gene expression in the liver as determined by the secretory pattern of GH and the role of STAT5 in body growth. Oncogene (2000).
Herrington
J
J
Department of Physiology, University of Michigan Medical School, Ann Arbor, Michigan, MI 48109-0622, USA.
Smit
L S
LS
Schwartz
J
J
Carter-Su
C
C
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D011986:Receptors, Somatotropin / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015843:Serpins; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D009687:Nuclear Proteins; D011986:Receptors, Somatotropin; C518910:SH2B1 protein, human; C492010:SH2B1 protein, rat; D050799:STAT5 Transcription Factor; C490400:Serpina3k protein, mouse; D015843:Serpins; D015534:Trans-Activators; D019382:Human Growth Hormone; D013006:Growth Hormone