Phosphorylation of the eIF4E-binding protein PHAS-I after exposure of PC12 cells to EGF and NGF.
PHAS-I or the eIF4E-binding protein 1 regulates the cap-binding activity of eIF4E by sequestering eIF4E. Binding of elF4E to PHAS-I is regulated by phosphorylation of PHAS-I. PC12 cells were used to study the signal transduction pathway leading to phosphorylation of PHAS-I. Both EGF and NGF induced phosphorylation of PHAS-I. Wortmannin, a PI-3 kinase inhibitor, staurosporine, a PKC inhibitor, and rapamycin, a FRAP inhibitor all blocked the phosphorylation of PHAS-I. Of the three inhibitors, only wortmannin was able to inhibit MAPK phosphorylation. This excludes a role for MAPK in NGF- and EGF-induced PHAS-I phosphorylation in PC12 cells. Apparently, PHAS-I was phosphorylated in a PI-3 kinase-, PKC-, and FRAP-dependent manner after EGF or NGF stimulation. Only PI-3 kinase and FRAP are involved in the regulation of the basal level of PHAS-I phosphorylation.
Utrecht University, Department of Molecular Cell Biology, The Netherlands. M.Kleijn@biol.ruu.nl
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Thomas
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D039561:Eukaryotic Initiation Factor-4E; D020104:Immunophilins; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D010448:Peptide Initiation Factors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction; D020123:Sirolimus; D019311:Staurosporine / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin
D000730:Androstadienes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D039561:Eukaryotic Initiation Factor-4E; D020104:Immunophilins; D047908:Intracellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D010448:Peptide Initiation Factors; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D019311:Staurosporine; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin; C499526:Eif4ebp1 protein, rat; C546845:mTOR protein, rat