Wu M Y, Hsu T L, Lin W W, Campbell R D, Hsieh S L
Department of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei 11221, Taiwan.
J Biol Chem. 1997 Jul 4;272(27):17154-9. doi: 10.1074/jbc.272.27.17154.
The lymphotoxin-beta receptor (LT-betaR) has been shown to be the receptor for the membrane-bound lymphotoxin heterotrimers LTalpha1/beta2 and LTalpha2/beta1. The extracellular domain of LT-betaR shows extensive similarity with members of the tumor necrosis factor receptor family, while its cytoplasmic domain is distinct and lacks any inherent enzymatic activity. This suggests that the interaction of LT-betaR with other molecules might be important for signal transduction. Here we demonstrate the association of a fusion protein, comprising glutathione S-transferase and the cytoplasmic domain of LT-betaR (GST-LT-betaR(CD)), with several proteins in the size range 29-80 kDa from HepG2 cell lysates. We present evidence that two of these proteins are serine/threonine kinases, which associate with amino acids 324-377 of the cytoplasmic domain of LT-betaR and phosphorylate this receptor. The characteristics of these novel kinases indicate that they are distinct from the previously described tumor necrosis factor receptor-associated kinases. This suggests the presence of novel signal transduction pathway(s) for LT-betaR.
淋巴毒素-β受体（LT-βR）已被证明是膜结合型淋巴毒素异源三聚体LTα1/β2和LTα2/β1的受体。LT-βR的胞外结构域与肿瘤坏死因子受体家族成员具有广泛的相似性，而其胞质结构域则不同，且缺乏任何内在的酶活性。这表明LT-βR与其他分子的相互作用可能对信号转导很重要。在这里，我们展示了一种融合蛋白，其由谷胱甘肽S-转移酶和LT-βR的胞质结构域（GST-LT-βR(CD)）组成，与来自HepG2细胞裂解物的几种大小在29-80 kDa范围内的蛋白质相关联。我们提供的证据表明，其中两种蛋白质是丝氨酸/苏氨酸激酶，它们与LT-βR胞质结构域的324-377位氨基酸相关联并使该受体磷酸化。这些新型激酶的特征表明它们与先前描述的肿瘤坏死因子受体相关激酶不同。这表明存在LT-βR的新型信号转导途径。
