Signal transduction through extracellular signal-regulated kinase-like pp57 blocked in differentiated cells having low protein kinase C beta activity.
pp57 is a cytoplasmic kinase which is related antigenically and functionally to the extracellular signal regulated kinase or the mitogen-activated kinase family of signal transduction proteins. Two undifferentiated colon carcinoma cell lines responded to the diacylglycerol diolein by growth and a rapid 3-4-fold increase in tyrosine phosphorylation of pp57, and smaller increases in threonine and serine phosphorylation. By enhancing tyrosine phosphorylation of pp57, diolein increased pp57 kinase activity on myelin basic protein. Two enterocytic differentiated colon carcinoma cell lines, when treated with diolein, exhibited neither increased pp57 tyrosine phosphorylation nor increased growth. Both enterocytic lines exhibited 30% of the total PKC activity, 10-20% of the abundance of PKC beta as detected by Western blotting with anti-peptide antisera, and 10-20% of the PKC beta activity, by immune complex kinase reactions, that was expressed in the undifferentiated cell lines. The abundance of three other PKC isozymes, alpha, epsilon, and zeta appeared unchanged in the undifferentiated and enterocytic lines, reflecting their common parental cell line origin. The association between loss of PKC beta activity and blocked signaling through pp57 in each of two cell lines suggests that PKC beta is part of a signal transduction system activating pp57.
Laboratory of GI Tumor Biology, Memorial Sloan Kettering Cancer Center, New York, New York 10021.
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Lee
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Ghose-Dastidar
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Winawer
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E
Friedman
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020572:Oncogene Proteins v-rel; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D004075:Diglycerides; D007527:Isoenzymes; D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic; D014443:Tyrosine; D011494:Protein Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C013965:diolein