Differentiation-dependent Suppression of Platelet-derived Growth Factor Signaling in Cultured Adipocytes

摘要: A critical component of vertebrate cellular differentiation is the acquisition sensitivity to a restricted subset peptide hormones and growth factors. This accounts for unique capability insulin (and possibly insulin-like factor-1), but not other factors, stimulate glucose uptake anabolic metabolism in heart, skeletal muscle, adipose tissue. selectivity faithfully recapitulated cultured adipocyte line, 3T3-L1, which responds insulin, platelet-derived factor (PDGF), with increased hexose uptake. The serine/threonine protein kinases Akt1 Akt2, have been implicated as mediators insulin-stimulated uptake, well glycogen, lipid, synthesis, were shown mirror this tissue culture system. was particularly apparent 3T3-L1 adipocytes overexpressing an epitope-tagged form Akt2 activated 10-fold better than PDGF. Similarly, adipocytes, only stimulated phosphorylation Akt's endogenous substrate, GSK-3β. Other signaling molecules, including phosphatidylinositol 3-kinase, pp70 S6-kinase, mitogen-activated kinase, PHAS-1/4EBP-1, did demonstrate selective responsiveness instead comparably by both Moreover, concurrent treatment PDGF diminish activation Akt, or transport, indicating that simultaneously activate inhibitory mechanism. Interestingly, Akt isoforms, numerous undifferentiated preadipocytes. Collectively, these data suggest differential may contribute insulin's exclusive mediation metabolic events involved metabolism. they novel mechanism differentiation-dependent hormone conferred through suppression specific pathways operational cell types.