Volume 272, Number 44, Issue of October 31, 1997 pp. 27660-27664
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

In Vivo Regulation of CrkII and CrkL Proto-oncogenes in the Uterus by Insulin-like Growth Factor-I
DIFFERENTIAL EFFECTS ON TYROSINE PHOSPHORYLATION AND ASSOCIATION WITH PAXILLIN

(Received for publication, April 11, 1997, and in revised form, July 31, 1997)

Andrew A. Butler , Vicky A. Blakesley , Anatolii Koval , Ron deJong , John Groffen and Derek LeRoith

From the  Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1770 and the Section on Molecular Carcinogenesis, Department of Pathology, Childrens Hospital, Los Angeles, California 90027

Changes in CrkII and CrkL phosphorylation are associated with insulin-like growth factor receptor activation in cultured cells. We examined whether similar changes also occur following administration of recombinant human insulin-like growth factor-I to the intact animal. In female rats starved overnight, CrkL phosphorylation was significantly increased 12 min after insulin-like growth factor-I administration. Tyrosine phosphorylation of CrkII was not detectable in either control or treated animals. Paxillin, a 65-70-kDa phosphoprotein containing high affinity binding sites common for the Src homology 2 (SH2) domains of CrkII and CrkL, was observed in both CrkII and CrkL immunoprecipitates. Insulin-like growth factor-I treatment stimulated the association of CrkII with paxillin. In contrast, the same treatment resulted in the dissociation of the CrkL-paxillin complex. Similar effects of insulin-like growth factor-I treatment on the association of CrkL with tyrosine phosphorylated paxillin were observed in fibroblasts overexpressing CrkL. This study demonstrates that the activation of the insulin-like growth factor-I receptor induces changes in the tyrosine phosphorylation and protein-protein interactions of the Crk proteins in vivo. The different responses of CrkL and CrkII to insulin-like growth factor-I receptor activation suggest distinct roles for these two adapter proteins in signal transduction.

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