Differential regulation of oncogenic and cellular p185 by serine/threonine kinases.
185c-neu is a member of a family of growth factor receptors with tyrosine kinase activity. A point mutation in the transmembrane region leads to activation of the enzymatic domain. We demonstrate that TPA (phorbol-12-myristate-13-acetate) stimulates the phosphorylation of p185c-neu on serine and threonine residues coincident with the inhibition of its intrinsic tyrosine kinase and the proliferation of cells that express it. The tyrosine kinase activity as well as the phosphorylation pattern of serine and threonine residues of oncogenic p185 (p185neu) and the growth of p185neu-expressing cells are not influenced by TPA. These observations indicate that the functional activity of p185c-neu can be regulated through protein kinase C (PKC) but the transmembrane point mutation present in p185neu renders it refractory to serine/threonine kinase regulation.
Dobashi
K
K
Department of Pathology, University of Pennsylvania, Philadelphia 19104-6082.
Weiner
D B
DB
Greene
M I
MI
D002455:Cell Division; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D012694:Serine / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013912:Threonine / Q000378:metabolism
D004815:Epidermal Growth Factor; D008565:Membrane Proteins; D015513:Oncogene Proteins; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D012694:Serine; D013755:Tetradecanoylphorbol Acetate; D013912:Threonine