Weinmaster G, Lemke G
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, San Diego, CA 92138.
EMBO J. 1990 Mar;9(3):915-20. doi: 10.1002/j.1460-2075.1990.tb08189.x.
Cyclic AMP (cAMP) cooperates with a wide variety of polypeptide growth factors to synergistically stimulate the proliferation of many vertebrate cell types. However, the cellular mechanisms underlying these cooperative interactions are for the most part unknown. We have identified one such mechanism by observing that (i) cultured rat Schwann cells proliferate in response to platelet-derived growth factor (PDGF) only if simultaneously cultured in the presence of agents that elevate intracellular cAMP and (ii) this unmasked PDGF response is accounted for by a dramatic cAMP-mediated induction of PDGF receptor mRNA and protein. cAMP-mediated induction of the PDGF receptor results in enhanced, ligand dependent receptor autophosphorylation, and in enhanced PDGF activation of c-fos gene expression. In addition, this induction is unique to those cells, such as Schwann cells, for which cAMP is itself mitogenic. These results indicate that the synergistic proliferative effect obtained from the combination of cAMP and polypeptide growth factors may in large result from the cAMP-mediated induction of growth factor receptors.
环磷酸腺苷（cAMP）与多种多肽生长因子协同作用，以协同刺激多种脊椎动物细胞类型的增殖。然而，这些协同相互作用背后的细胞机制在很大程度上尚不清楚。我们通过观察发现了一种这样的机制：（i）培养的大鼠雪旺细胞仅在同时存在能提高细胞内cAMP的试剂的情况下，才会对血小板衍生生长因子（PDGF）作出增殖反应；（ii）这种被揭示的PDGF反应是由cAMP介导的PDGF受体mRNA和蛋白的显著诱导所导致的。cAMP介导的PDGF受体诱导导致增强的、配体依赖性受体自磷酸化，以及增强的c-fos基因表达的PDGF激活。此外，这种诱导对于那些cAMP本身具有促有丝分裂作用的细胞（如雪旺细胞）来说是独特的。这些结果表明，从cAMP和多肽生长因子的组合中获得的协同增殖效应可能很大程度上是由cAMP介导的生长因子受体诱导所致。
