CrkII participation in the cellular effects of growth hormone and insulin-like growth factor-1. Phosphatidylinositol-3 kinase dependent and independent effects

Eyleen L K Goh, Tao Zhu, Shoshana Yakar, Derek LeRoith, Peter E. Lobie

Research output: Contribution to journalArticle

Abstract

We have examined the role of CrkII in the cellular response to both human growth hormone (hGH) and human insulin-like growth factor-1 (hIGF-1). We have demonstrated that overexpression of the adaptor molecule enhances both basal phosphatidylinositol 3-kinase (PI 3-kinase) activity and also dramatically enhances the ability of both hormones to stimulate PI 3-kinase activity in the cell. Many of the effects of CrkII overexpression on hGH- and hIGF-1-stimulated cellular function can then be attributed to CrkII enhancement of PI 3-kinase stimulation by these hormones. Thus, CrkII- enhan+ced PI 3-kinase activity is used to enhance actin filament reorganization in response to both hGH and hIGF-1, to enhance stress activated protein kinase (SAPK) activity in response to hGH, and to diminish STAT5-mediated transcription in response to hGH. It is apparent, however, that CrkII also regulates cellular function independent of its ability to stimulate PI 3-kinase activity. This is evidenced by the ability of CrkII, in a PI 3-kinase-independent manner, to diminish the activation of p44/42 mitogen-activated protein kinase in response to both hGH and hIGF-1 and to inhibit the activation of SAPK by hIGF-1. Therefore, despite the common use of CrkH to activate PI 3-kinase, CrkII also allows hGH or hIGF-1 to selectively switch the activation of SAPK. Thus, common utilization of CrkII by hGH and hIGF-1 allows the execution of common cellular effects of these hormones, concomitant with the retention of hormonal specificity.

Original languageEnglish (US)
Pages (from-to)17683-17692
Number of pages10
JournalJournal of Biological Chemistry
Volume275
Issue number23
DOIs
StatePublished - Jun 9 2000

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Phosphatidylinositol 3-Kinase
Human Growth Hormone
Somatomedins
Growth Hormone
Heat-Shock Proteins
Protein Kinases
Chemical activation
Hormones
Transcription
Mitogen-Activated Protein Kinases
Actin Cytoskeleton
Actins
Switches
Molecules

ASJC Scopus subject areas

  • Biochemistry

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CrkII participation in the cellular effects of growth hormone and insulin-like growth factor-1. Phosphatidylinositol-3 kinase dependent and independent effects. / Goh, Eyleen L K; Zhu, Tao; Yakar, Shoshana; LeRoith, Derek; Lobie, Peter E.

In: Journal of Biological Chemistry, Vol. 275, No. 23, 09.06.2000, p. 17683-17692.

Research output: Contribution to journalArticle

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