Kawabata M, Imamura T, Miyazono K, Engel M E, Moses H L
Vanderbilt Cancer Center, Nashville, Tennessee 37232-6838, USA.
J Biol Chem. 1995 Dec 15;270(50):29628-31. doi: 10.1074/jbc.270.50.29628.
Transforming growth factor-beta 1 (TGF-beta 1) is the prototype of a large family of molecules that regulate a variety of biological processes. The type I (T beta R-I) and type II (T beta R-II) receptors for TGF-beta 1 are transmembrane serine/threonine kinases, forming a heteromeric signaling complex. Recent studies have shown that T beta R-II is a constitutively active kinase and phosphorylates T beta R-I upon ligand binding, suggesting that T beta R-I is the effector subunit of the receptor complex, which transduces signals to intracellular targets. This model has been further confirmed by the identification of constitutively active T beta R-I that mediates TGF-beta 1-specific cellular responses in the absence of ligand and T beta R-II. To investigate signaling by TGF-beta 1, we have sought to isolate proteins that interact with the cytoplasmic region of T beta R-I. One of the proteins identified was the alpha subunit of farnesyl-protein transferase (FT alpha) that modifies a series of peptides including Ras. T beta R-I specifically interacts with FT alpha in the yeast two-hybrid system. Glutathione S-transferase-T beta R-I fusion proteins bind FT alpha translated in vitro. T beta R-I also phosphorylates FT alpha. We further show that the constitutively active T beta R-I interacted with FT alpha very strongly whereas an inactive form of T beta R-I did not. These results suggest that FT alpha may be one of the substrates of the activated T beta R-I kinase.
转化生长因子-β1（TGF-β1）是一大类调节多种生物学过程的分子的原型。TGF-β1的I型受体（TβR-I）和II型受体（TβR-II）是跨膜丝氨酸/苏氨酸激酶，形成异源信号复合物。最近的研究表明，TβR-II是一种组成型活性激酶，在配体结合时磷酸化TβR-I，这表明TβR-I是受体复合物的效应亚基，可将信号转导至细胞内靶点。通过鉴定在没有配体和TβR-II的情况下介导TGF-β1特异性细胞反应的组成型活性TβR-I，这一模型得到了进一步证实。为了研究TGF-β1的信号传导，我们试图分离与TβR-I细胞质区域相互作用的蛋白质。鉴定出的其中一种蛋白质是法尼基蛋白转移酶（FTα）的α亚基，它修饰包括Ras在内的一系列肽。在酵母双杂交系统中，TβR-I与FTα特异性相互作用。谷胱甘肽S-转移酶-TβR-I融合蛋白与体外翻译的FTα结合。TβR-I也使FTα磷酸化。我们进一步表明，组成型活性TβR-I与FTα的相互作用非常强烈，而无活性形式的TβR-I则不然。这些结果表明，FTα可能是活化的TβR-I激酶的底物之一。
