Linked Life Data

9076344

Source:http://linkedlifedata.com/resource/pubmed/id/9076344

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-5-22
pubmed:abstractText
GH has long been known as a regulator of body growth and metabolism, yet its mechanism of action at the cellular level has been elusive. We have recently shown that GH promotes the rapid association of GH receptor with the tyrosine kinase JAK2, activates JAK2, and promotes the tyrosyl phosphorylation of both JAK2 and GH receptor. This suggests that the initial signalling event in GH action is the activation of JAK2 which in turn phosphorylates tyrosines within JAK2 and GH receptor. We have identified a number of proteins that appear to bind to these phosphotyrosines in GH receptor/ JAK2 complexes. These proteins in turn become phosphorylated on tyrosines, resulting in their activation. These proteins include: 1) the signal transducers and activators of transcriptions (Stats) 1, 3 and 5 which have been implicated as regulators of transcription of a variety of genes; 2) the insulin receptor substrates (IRS) 1 and 2, which are believed to mediate some of the metabolic effects of GH; and 3) Shc proteins which lie upstream of Ras and the mitogen activator kinases (MAP) designated ERKs 1 and 2, proteins implicated in the regulation of cellular growth and/or differentiation. These various proteins work in concert with each other and with other signalling molecules to elicit the diverse effects of GH. Other hormones and growth factors also activate JAK kinases. Specificity in signalling was investigated by determining whether signalling pathways for particular ligands may be selectively inhibited by hormones or growth factors. Glucocorticoids were found to selectively decrease binding and cellular signalling in response to GH. This decrease appeared to be due to a decrease in the number of GH receptors in the plasma membrane. Using truncated and mutated GHR, two regions of the GH receptor were identified required for the inhibitory effect of glucocorticoids. Interestingly, they appeared to differ from the region required for GH-induced internalization. Hence, a large amount of insight into signalling by GH has been obtained during the 3 years since JAK2 was identified as a signalling molecule for GH and other ligands that bind to members of the cytokine receptor family. This new insight, and the insight that will continue to be gained in the next few years should enable the design of new and better therapeutic uses of GH and the other ligands that bind to JAK kinase-linked receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0918-8959
pubmed:author
pubmed:issnType
Print
pubmed:volume
43 Suppl
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S65-70
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Signalling pathway of GH.
pubmed:affiliation
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review