Two Forms of Microtubule-Associated Protein Kinase Are Commonly Involved in Signal Transduction Pathways Induced by Various Growth Factors

Abstract

Nerve growth factor (NGF)- and epidermal growth factor (EGF)-stimulated microtubule-associated protein (MAP) kinase activities from PC-12 cells were recently found to be resolvable into two peaks (MAP kinases I and II) by ion-exchange or hydrophobic-interaction HPLC. To compare MAP kinases detected in PC-12 cells with growth factor-sensitive MAP kinases in other cells, a number of tissue culture cells were treated with various growth factors such as NGF, EGF, platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and endothelial cell growth factor (ECGF); and lysates of the cells were assayed for MAP kinase activity. Cells transfected with the NGF receptor gene (CHO-1Q) and those overexpressing the EGF receptor (A-431) had a high background level of MAP kinase activities. On the other hand, overexpression of tyrosine kinase activities causes the down regulation and the desensitization of the growth factor responses in SR-3Y1 and trk-3T3 cells. No detectable EGF receptor was observed in SR-3Y1 and trk-3T3 cells. The level of MAP kinases I and II activation by growth factors was cell line dependent, but the two forms of MAP kinases, I and II, were detected in all cultured cells examined and activated by various growth factors. These data suggest that the activation of these two forms of MAP kinase are commonly involved in the signal transduction pathways induced by various growth factors.