Growth hormone signalling and its regulation: preventing too much of a good thing.
Growth hormone (GH) is a major growth-promoting and metabolic regulatory hormone. Interaction of GH with its cell surface GH receptor (GHR), by virtue of receptor dimerization, causes activation of the GHR-associated cytoplasmic tyrosine kinase, JAK2. Several signalling pathways, including the STAT5, PI3 kinase and MAP kinase pathways, are thereby accessed, resulting in various biochemical and biological cellular signalling outcomes which are rapidly becoming deciphered. Various mechanisms probably exist to terminate, modulate and prevent GH signalling. Some of these mechanisms regulate receptor abundance and/or availability while others may alter the responsiveness of downstream signalling molecules to receptor engagement. In this review, recent insights into modulation of GH signalling are discussed. Special emphasis is placed on mechanisms of homologous and heterologous desensitization and on the likelihood that inducible GHR proteolysis, in addition to causing GH binding protein generation, may also serve as an important mechanism of heterologous GHR downregulation.
Frank
S J
SJ
Department of Medicine, Division of Endocrinology and Metabolism, University of Alabama at Birmingham, 1530 3rd Avenue South, BDB 861, Birmingham, AL 35294-0012, USA. frank@endo.dom.uab.edu
D000818:Animals; D019281:Dimerization; D015536:Down-Regulation; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D011986:Receptors, Somatotropin / Q000378:metabolism; D015398:Signal Transduction
D011986:Receptors, Somatotropin; D013006:Growth Hormone