Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae

The ability of a peptide hormone to affect many different intracellular targets is thought to be possible because of the modular organization of signal transducing molecules in the cell. Evidence for the presence of signaling modules in metazoan cells, however, is incomplete. Herein we show, with morphology and cell fractionation, that all the components of a mitogen-activated protein kinase pathway are concentrated in caveolae of unstimulated human fibroblasts. Addition of platelet-derived growth factor to either the intact cell or caveolae isolated from these cells stimulates tyrosine phosphorylation and activates mitogen-activated protein kinases in caveolae. The molecular machinery for kinase activation, therefore, is preorganized at the cell surface of quiescent cells.

人们普遍认为，肽激素可对多种不同细胞内靶点产生调控作用，其分子基础在于细胞内信号转导分子的模块化组织。然而，目前关于多细胞动物细胞中存在信号转导模块的相关证据仍不充分。本文通过形态学分析与细胞分级分离实验证实：未受刺激的人成纤维细胞的膜穴（caveolae）中富集有丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）通路的所有组分。无论是向完整细胞施加血小板衍生生长因子（platelet-derived growth factor，PDGF），还是将其作用于从该类细胞中分离得到的膜穴，均可引发酪氨酸磷酸化反应，并激活膜穴内的丝裂原活化蛋白激酶。由此可见，介导激酶激活的分子机器，在静息细胞的细胞表面已预先组装完备。