Tyrosine kinase activity of a chimeric insulin-like-growth-factor-1 receptor containing the insulin receptor C-terminal domain. Comparison with the tyrosine kinase activities of the insulin and insulin-like-growth-factor-1 receptors using a cell-free system.

In a previous study, we showed that a chimeric insulin-like-growth-factor-1 (IGF-1) receptor, with the beta subunit C-terminal part of the insulin receptor was more efficient in stimulating glycogen synthesis and p44mapk activity compared to the wild-type IFG-1 receptor [Tartare, S., Mothe, I., Kowalski-Chauvel, A.

Signal transduction by a chimeric insulin-like growth factor-1 (IGF-1) receptor having the carboxyl-terminal domain of the insulin receptor.

Insulin-like growth factor-1 receptors (IGF-1R) and insulin receptors (IR) are closely related tyrosine kinases. However, the IR plays a major role in metabolism control, whereas the IGF-1R is mainly involved in growth and differentiation. With these observations in mind, we wished to define the regions of IR and IGF-1R responsible for generation of biological specificity.

Cross talk among tyrosine kinase receptors in PC12 cells: desensitization of mitogenic epidermal growth factor receptors by the neurotrophic factors, nerve growth factor and basic fibroblast growth factor.

We have studied the effects of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) on epidermal growth factor (EGF) binding to PC12 cells. We show that NGF and bFGF rapidly induce a reduction in 125I-EGF binding to PC12 cells in a dose-dependent manner. This decrease amounts to 50% for NGF and 35% for bFGF.

The insulin and insulin-like growth factor-I receptor substrate IRS-1 associates with and activates phosphatidylinositol 3-kinase in vitro.

Phosphatidylinositol 3-kinase (PtdIns-3-kinase) is thought to participate in the transductional cascade used by several tyrosine kinase receptors including the insulin-like growth factor (IGF)-I receptor and the insulin receptor. The major insulin receptor cellular substrate IRS-1 (pp185) has been proposed as a possible link between the insulin receptor and PtdIns-3-kinase. In this study we show that both insulin and IGF-I treatment of murine fibroblasts transfected with insulin or IGF-I receptors increase PtdIns-3-kinase activity immunoprecipitated with an antibody directed against the 85-kDa subunit of PtdIns-3-kinase.

[The insulin receptor: mechanism of activation and message transmission].

The insulin receptor is a heterotetrameric glycoprotein composed of two 130 kD extracellular alpha subunits and two 95 kD membrane-spanning beta subunits. The insulin receptor functions as an allosteric enzyme which undergoes conformational changes when its alpha subunit binds insulin, resulting in activation and autophosphorylation of the tyrosine kinase contained in the beta subunit. This receptor activation is due to intermolecular reactions responsible for amplification of the hormone-induced response at the receptor level.