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Horoscope explorer pro 5.02 download link.Positive selection: in vitro and in vivo studies on insulin-like growth factor I receptor mutants.

Mutations in the insulin-like growth factor I (IGF-I) receptor can result in a spectrum of phenotypes, ranging from severe hypoglycaemia to skeletal dysplasia. We have demonstrated that the majority of mutations causing hypoglycaemia are neutral with respect to ligand binding (r) and signal transduction (kd), and that they are frequently associated with gain of function on one or both (binding and signalling) parameters. However, this observation is not specific to the IGF-I receptor, and similar observations can be made for other growth factor receptors with tyrosine kinase activity. We have identified a small number of mutations in the IGF-I receptor which are associated with loss of function (negative selection) or impairment of ligand binding or signal transduction in vitro (gain of function). We have shown that expression of the normally rare autosomal dominant IGF-I receptor mutations in NIH 3T3 cells results in cell transformation. Furthermore, cells transformed with these autocrine receptor mutants have a selective disadvantage in vivo relative to wild-type IGF-I receptor cells. These findings argue that the increase in tyrosine kinase activity associated with some of the IGF-I receptor mutants is deleterious and that autocrine signalling by these receptors is responsible for their neoplastic transformation. if (!$fields) {

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