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Volume 271, Number 46, Issue of November 15, 1996 pp. 28960-28968
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Reduced Cell Attachment and Phosphorylation of Focal Adhesion Kinase Associated with Expression of a Mutant Insulin Receptor

(Received for publication, July 8, 1996, and in revised form, August 13, 1996)

From the University of Melbourne, Department of Medicine, P. O. Royal Melbourne Hospital, Parkville 3050 and ^§ Deakin University, Institute of Human Nutrition, Malvern, 3144 Victoria, Australia

Insulin signaling results in rapid changes to the cell cytoskeleton, and it has recently been shown that insulin stimulates the dephosphorylation of the cytoskeletal-associated tyrosine kinase, focal adhesion kinase (pp125^FAK). We report here that mutation of two tryptic cleavage sites (Lys¹⁶⁴ and Lys⁵⁸²  Asn; 2N) in the insulin receptor -subunit results in a cell-line (CHO.2N-10) with altered morphology associated with an increase in cell size, a decrease in cell adhesiveness, and a decrease in pp125^FAK tyrosine phosphorylation in the absence of insulin (45.2 ± 9.7% compared to nontransfected Chinese hamster ovary (CHO) cells). In contrast to pp125^FAK, paxillin phosphorylation was similar in all cell lines despite lower levels (61.0 ± 10.4% compared to CHO cells) of paxillin protein in CHO.2N-10 cells. We observed comparable protein levels of pp125^FAK and the structural focal adhesion protein, vinculin, in all cell lines. Despite underphosphorylation of pp125^FAK in the basal state, insulin stimulation of CHO.2N-10 cells still resulted in dephosphorylation of pp125^FAK. CHO.2N-10 and CHO.T (overexpress wild-type insulin receptor) cells have similar insulin binding characteristics, insulin-stimulated autokinase and peptide phosphorylation, and insulin-stimulated pp185/IRS-1 phosphorylation. Our results suggest that the insulin receptor may play an important role in cell-matrix interactions, such as modulating cell adhesion and inducing cell architecture changes.

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