Coughlin S R, Lee W M, Williams P W, Giels G M, Williams L T
Cell. 1985 Nov;43(1):243-51. doi: 10.1016/0092-8674(85)90029-7.
The role of the phosphoinositide turnover-protein kinase C pathway in mediating PDGF-stimulated c-myc expression and cell proliferation was studied. Both direct activators of kinase C (e.g. phorbol ester analogues) and hormones that activate kinase C via receptor-mediated phosphoinositide turnover (e.g. PDGF, bradykinin, or vasopressin) elicited a rapid increase in c-myc mRNA expression. Desensitization of the kinase C pathway by prolonged exposure to phorbol abolished the induction of c-myc by subsequent phorbol challenge and attenuated c-myc induction by PDGF and bradykinin, but did not affect PDGF-stimulated mitogenesis. Bradykinin and phorbol esters stimulated the same magnitude of c-myc expression as PDGF but elicited less than one-tenth the PDGF-induced mitogenic response. We conclude that stimulation of c-myc expression is a common response to a diverse group of agents that elicit phosphoinositide turnover and activate protein kinase C, and that neither activation of protein kinase C nor enhanced c-myc expression is sufficient for the mitogenic action of PDGF.
研究了磷酸肌醇转换-蛋白激酶C途径在介导血小板衍生生长因子（PDGF）刺激的c-myc表达和细胞增殖中的作用。蛋白激酶C的直接激活剂（如佛波酯类似物）以及通过受体介导的磷酸肌醇转换激活蛋白激酶C的激素（如PDGF、缓激肽或血管加压素）均能使c-myc mRNA表达迅速增加。通过长时间暴露于佛波醇使蛋白激酶C途径脱敏，可消除后续佛波醇刺激诱导的c-myc表达，并减弱PDGF和缓激肽诱导的c-myc表达，但不影响PDGF刺激的有丝分裂。缓激肽和佛波酯刺激的c-myc表达幅度与PDGF相同，但引发的有丝分裂反应不到PDGF诱导反应的十分之一。我们得出结论，c-myc表达的刺激是对引发磷酸肌醇转换并激活蛋白激酶C的多种试剂的常见反应，并且蛋白激酶C的激活或c-myc表达的增强都不足以产生PDGF的促有丝分裂作用。
