In vivo and in vitro serine/threonine phosphorylations of epidermal growth factor receptor upon entry into the cell cycle.
Protein phosphorylation and dephosphorylation is one of the main mechanisms of cell cycle regulation. This study examines the modulation of epidermal growth factor receptor phosphorylation as cells emerge from quiescence and enter the S phase of the cell cycle. The epidermal growth factor receptor is phosphorylated primarily on serine and threonine, but not on tyrosine residues, in an S phase-dependent fashion, as determined by phosphoamino acid analysis and anti-phosphotyrosine immunoblotting. These phosphorylations occur both in vitro and in vivo and are ligand independent. Some of the sites that are phosphorylated in vitro also appear to be phosphorylated in vivo, as determined by two-dimensional tryptic phosphopeptide analysis. At least one of the in vivo phosphorylation sites is phosphorylated by mitogen-activated protein kinase. Although the mechanism for this ligand-independent phosphorylation is not known, its correlation with emergence from quiescence and entry into the cell cycle suggests that the phosphorylation of epidermal growth factor receptor on serine and threonine residues may have heretofore unknown role(s) in cell cycle entry and progression.
Pillay
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Department of Microbiology and Immunology, University of Tennessee/Memphis 38163.
Sharma
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D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D016895:Culture Media, Serum-Free; D015180:Electrophoresis, Gel, Two-Dimensional; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007399:Interphase / Q000502:physiology; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016895:Culture Media, Serum-Free; D010748:Phosphopeptides; D010769:Phosphothreonine; D010768:Phosphoserine; D019000:Phosphotyrosine; D014443:Tyrosine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases