Jin Qunyan, Ding Wei, Staub Cory M, Gao Guofeng, Tang Qian, Mulder Kathleen M
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Cell Signal. 2005 Nov;17(11):1363-72. doi: 10.1016/j.cellsig.2005.02.004. Epub 2005 Mar 31.
We previously identified km23 as a novel TGFbeta receptor-interacting protein. Here we show that km23 is ubiquitously expressed in human tissues and that cell-type specific differences in endogenous km23 protein expression exist. In addition, we demonstrate that the phosphorylation of km23 is TGFbeta-dependent, in that EGF was unable to phosphorylate km23. Further, the kinase activity of both TGFbeta receptors appears to play a role in the TGFbeta-mediated phosphorylation of km23, although TGFbeta RII kinase activity is absolutely required for km23 phosphorylation. Blockade of km23 using small interfering RNAs significantly decreased key TGFbeta responses, including induction of fibronectin expression and inhibition of cell growth. Thus, our results demonstrate that km23 is required for TGFbeta induction of fibronectin expression and is necessary, but not sufficient, for TGFbeta-mediated growth inhibition.
我们先前鉴定出km23是一种新型的转化生长因子β（TGFβ）受体相互作用蛋白。在此我们表明，km23在人体组织中普遍表达，并且内源性km23蛋白表达存在细胞类型特异性差异。此外，我们证明km23的磷酸化是TGFβ依赖性的，因为表皮生长因子（EGF）无法使km23磷酸化。此外，尽管km23磷酸化绝对需要TGFβⅡ型受体（TGFβRII）激酶活性，但两种TGFβ受体的激酶活性似乎都在TGFβ介导的km23磷酸化中发挥作用。使用小干扰RNA阻断km23可显著降低关键的TGFβ反应，包括诱导纤连蛋白表达和抑制细胞生长。因此，我们的结果表明，km23是TGFβ诱导纤连蛋白表达所必需的，并且是TGFβ介导的生长抑制所必需但不充分的条件。
