Mundschau L J, Forman L W, Weng H, Faller D V
Boston University School of Medicine, Cancer Research Center, Massachusetts 02118.
J Biol Chem. 1994 Jun 10;269(23):16137-42.
Autophosphorylation of the platelet-derived growth factor (PDGF) receptor on tyrosine, which is dependent upon and occurs immediately after ligand binding, has been linked to the activation of second messenger pathways thought to be necessary for the induction of gene expression, DNA synthesis, and mitogenesis. We have investigated PDGF signal transduction in Balb/c3T3 and NIH-3T3 cells at the level of immediate-early gene induction under three conditions in which PDGF receptor autophosphorylation in response to PDGF binding is blocked: cells transformed by v-rasKi, cells transformed by v-mos, and cells treated with genistein, a specific inhibitor of tyrosine kinases. PDGF induction of immediate-early genes c-myc, c-fos, and JE is blocked in these systems. Induction of another immediate-early gene, egr-1, occurs normally despite the absence of measurable tyrosine kinase activity. The same results were obtained when cells were stimulated with PDGF-AA or PDGF-BB. It is not yet clear if this receptor tyrosine kinase-independent signal utilizes known PDGF second messengers, but these results demonstrate a new arm of the PDGF signal transduction pathway which operates in the absence of, and independently from, autophosphorylation of the receptor on tyrosine.
血小板衍生生长因子（PDGF）受体的酪氨酸自磷酸化依赖于配体结合，并在配体结合后立即发生，它与被认为是基因表达、DNA合成和有丝分裂诱导所必需的第二信使途径的激活有关。我们在三种条件下研究了Balb/c3T3和NIH-3T3细胞中PDGF信号转导在即时早期基因诱导水平的情况，这三种条件下响应PDGF结合的PDGF受体自磷酸化被阻断：被v-rasKi转化的细胞、被v-mos转化的细胞以及用酪氨酸激酶特异性抑制剂染料木黄酮处理的细胞。在这些系统中，PDGF对即时早期基因c-myc、c-fos和JE的诱导被阻断。尽管没有可测量的酪氨酸激酶活性，但另一个即时早期基因egr-1的诱导正常发生。当用PDGF-AA或PDGF-BB刺激细胞时，也得到了相同的结果。目前尚不清楚这种不依赖受体酪氨酸激酶的信号是否利用已知的PDGF第二信使，但这些结果证明了PDGF信号转导途径的一个新分支作用于不存在受体酪氨酸自磷酸化且独立于其的情况。
