The beta-PDGF receptor induces neuronal differentiation of PC12 cells.
Expression of the mouse beta-PDGF receptor by gene transfer confers PDGF-dependent and reversible neuronal differentiation of PC12 pheochromocytoma cells similar to that observed in response to NGF and basic FGF. A common property of the PDGF, NGF, and basic FGF-induced differentiation response is the requirement for constant exposure of cells to the growth factor. To test the hypothesis that a persistent level of growth factor receptor signaling is required for the maintenance of the neuronal phenotype, we examined the regulation of the serine/threonine-specific MAP kinases after either short- (10 min) or long-term (24 h) stimulation with growth factors. Mono Q FPLC resolved two peaks of growth factor-stimulated MAP kinase activity that coeluted with tyrosine phosphorylated 41- and 43-kDa polypeptides. MAP kinase activity was markedly stimulated (approximately 30-fold) within 5 min of exposure to several growth factors (PDGF, NGF, basic FGF, EGF, and IGF-I), but was persistently maintained at 10-fold above basal activity after 24 h only by the growth factors that also induce PC12 cell differentiation (PDGF, NGF, and basic FGF). Thus the beta-PDGF receptor is in a subset of tyrosine kinase-encoded growth factor receptors that are capable of maintaining continuous signals required for differentiation of PC12 cells. These signals include the constitutive activation of cytoplasmic serine/threonine protein kinases.
Heasley
L E
LE
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Johnson
G L
GL
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002454:Cell Differentiation / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016716:PC12 Cells; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D014443:Tyrosine
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D014443:Tyrosine; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases