Defective receptors for platelet-derived growth factor AA in human fibroblasts with mutant insulin receptors.
Leprechaunism is an inherited disorder characterized by growth restriction and severe insulin resistance and caused by mutations in the insulin receptor gene. Cells from these patients have defective insulin binding. Fibroblasts from some patients have concomitant defects in other tyrosine kinase receptors, such as those for Insulin-like Growth Factor I (IGF-I) and Epidermal Growth Factor (EGF). In this report, binding of insulin, IGF-I, EGF, and Platelet derived growth factor (PDGF) AA and PDGF-BB is compared among fibroblasts of patients with defined mutations in their insulin receptor gene. Fibroblasts from patient Atl-1, homozygous for a R86P substitution in the insulin receptor, had reduced binding of Platelet-Derived Growth Factor AA (PDGF-AA), a specific ligand for type alpha PDGF receptors. The reduction in PDGF binding impaired the ability of this growth factor to stimulate DNA synthesis.
Longo
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Department of Pediatrics, Emory University, Atlanta, GA 30322.
D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D000077214:Becaplermin; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D009154:Mutation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012016:Reference Values; D012867:Skin / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D007328:Insulin; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D004247:DNA; D011972:Receptor, Insulin; D017479:Receptors, Platelet-Derived Growth Factor; D013936:Thymidine