ISSN:
1573-4919
Keywords:
mitogenesis
;
insulin
;
tyrosine phosphorylation
;
phosphatase
;
neoplastic transformation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Insulin selectively induces mitogenesis in quiescent SV40 large T antigen-transformed murine 3T3T (CSV3-1) cells but not in quiescent nontransformed 3T3T cells. This mitogenic effect induced by insulin in CSV3-1 cells requires an induction of AP-1 activity associated with c-Jun and JunB. To further investigate the mechanisms that are involved in insulin-induced mitogenesis in CSV3-1 cells, the current experiments were performed. The results show that following insulin stimulation, the insulin receptor β-subunit and the insulin receptor substrate-1 undergo a much more significant tyrosine phosphorylation in CSV3-1 cells than in 3T3T cells. Insulin also induces tyrosine phosphorylation of a 73 kDa protein that is coprecipitated with the tyrosine-phosphorylated insulin receptor in CSV3-1 cells but not in 3T3T cells. The increased tyrosine phosphorylation in response to insulin stimulation in CSV3-1 cells does not appear to be due to an increase in the level of expression of the insulin receptor and does not appear to result from a significant change in tyrosine phosphatase activity compared to nontransformed cells. The results also show that the insulin effect in CSV3-1 cells is not mediated by insulin-like growth factor 1 receptor because insulin at the concentrations that induce mitogenesis does not increase the tyrosine phosphorylation of the insulin-like growth factor 1 receptor and the expression level of the receptor is not significantly changed in CSV3-1 cells compared to nontransformed cells. These data together indicate that the selective mitogenic effect of insulin on CSV3-1 cells involves increased tyrosine phosphorylation of the insulin receptor, the insulin receptor substrate-1 and the 73 kDa protein, although the underlying mechanisms need to be further elucidated.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1006937720559
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