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Vol. 9, Issue 11, 3057-3069, November 1998
Programme in Cell Biology, The Hospital for Sick Children, Toronto,
Ontario, Canada M5G 1X8
Insulin can regulate the abundance and organization of filamentous
actin within cells in culture. Early studies using cell lines that
overexpress the insulin receptor demonstrated that insulin caused a
rapid reversible disassembly of actin filaments that coincided with the
rapid tyrosine dephosphorylation of focal adhesion kinase. We have
extended these studies by demonstrating that paxillin, another focal
adhesion protein, and Src undergo tyrosine dephosphorylation in
response to insulin in Chinese hamster ovary (CHO) and rat hepatoma
(HTC) cells that overexpress the insulin receptor. This contrasted with
the effect of insulin in parental CHO and HTC cells in which focal
adhesion proteins were not dephosphorylated in response to the hormone.
In addition, insulin caused a dispersion of focal adhesion proteins and
disruption of actin filament bundles only in cells that overexpressed
the insulin receptor. Moreover, in 3T3-L1 adipocytes, which are
considered prototypic insulin-responsive cells, actin filament assembly
was stimulated, and focal adhesion protein tyrosine phosphorylation was
not altered. 3T3-L1 cells have more insulin receptors than either
parental CHO or HTC cells but have fivefold less insulin receptors than
the overexpressing cell lines. We hypothesize that a threshold may
exist in which the overexpression of insulin receptors determines how
insulin signaling pathways regulate the actin cytoskeleton.
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