Abstract: |
Basic fibroblast growth factor (FGF) induced a rapid increase in tyrosine phosphorylation of a 57-kDa cytoplasmic protein with functional myelin basic protein kinase activity and antigenic properties common to mitogen-activated kinases or extracellular signal-regulated kinases. Basic and acidic FGFs and the diacylglycerol diolein used the same signal transduction pathway to activate pp57. These FGFs, like diolein (Lee, H., Ghose-Dastidar, J., Winawer, S., and Friedman, E. (1993) J. Biol. Chem., 268, 5255-5263), increased the cellular concentration of long-chain diacylglycerols within the same short time period as they increased pp57 tyrosine phosphorylation. Both FGF and diolein increased phosphorylation of pp57 on the same V8 protease- generated fragments, suggesting a common pathway for the phosphorylation of pp57. FGF-induced signal transduction through pp57 mitogen-activated kinase led to cell growth in two undifferentiated colon carcinoma cell lines. In contrast, basic FGF neither increased tyrosine phosphorylation of pp57 nor increased cell growth in two colon goblet cell differentiated lines derived from the same parental line as the undifferentiated cells. Both goblet cell lines exhibited levels of protein-tyrosine kinase activity about one-fifth that of the undifferentiated lines. The decrease in tyrosine kinase activity was not due to down-regulation of FGF receptors or their tyrosine kinase activities. c-src kinase-specific activity was decreased 4-5-fold in both goblet cell lines, suggesting a role for c-src in pp57-mediated signal transduction. |
Keywords: |
signal transduction; platelet derived growth factor; controlled study; protein phosphorylation; human cell; cell growth; protein kinases; colonic neoplasms; cell differentiation; tumor cells, cultured; enzyme activity; protein tyrosine kinase; tyrosine; fibroblast growth factor 2; kinetics; insulin; proteinase; colon carcinoma; molecular weight; clone cells; carcinoma cell; diacylglycerol; fibroblast growth factor; transforming growth factor alpha; diglycerides; goblet cell; mitogenic agent; phorbol 13 acetate 12 myristate; basic fibroblast growth factor; fibroblast growth factor receptor; receptors, fibroblast growth factor; fibroblast growth factor 1; protein-tyrosine kinase; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; genes, src; acidic fibroblast growth factor; proto-oncogene protein pp60(c-src); glycerol dioleate
|