TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton
TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton
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DOI：
10.1074/jbc.274.43.30729
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发表时间：
1999-10-22
影响因子：
4.8
通讯作者：
Luo, Y
中科院分区：
文献类型：
--
作者：
Fu, CA;Shen, M;Luo, Y
GCK是Ste 20激酶家族的一个亚组。在这里，我们描述了一个新的GCK家族激酶，Traf 2和NCK相互作用的激酶（TNIK），与Traf 2和NCK相互作用的克隆和表征。TNIK编码具有8种剪接异构体的1360个氨基酸的多肽。它在N-末端激酶结构域和C-末端生发中心激酶同源区中与Nck相互作用激酶具有90%的氨基酸同一性。在中间区域同源性下降到53%。当转染到Phoenix-A细胞（293细胞的衍生物）中时，TNIK特异性激活c-Jun N末端激酶途径，这与许多GCK类似。然而，与其他GCK相反，这种激活仅由TNIK的GCK同源区介导。此外，在Phoenix-A、NIH-3 T3和Hela细胞中，野生型TNIK的过表达，而非TNIK的激酶突变形式，导致F-肌动蛋白结构的破坏和细胞扩散的抑制。此外，TNIK可以在体外磷酸化凝溶胶蛋白。这是首次发现GCK家族激酶可能参与细胞骨架的调节。
Germinal center kinases (GCKs) compose a subgroup of the Ste20 family of kinases. Here we describe the cloning and characterization of a novel GCK family kinase, Traf2- and Nck-interacting kinase (TNIK) that interacts with both Traf2 and Nck. TNIK encodes a polypeptide of 1360 amino acids with eight spliced isoforms. It has 90% amino acid identity to the Nck-interacting kinase in both the N-terminal kinase domain and the C-terminal germinal center kinase homology region. The homology drops to 53% in the intermediate region. TNIK specifically activates the c-Jun N-terminal kinase pathway when transfected into Phoenix-A cells (derivatives of 293 cells), similar to many GCKs. However, in contrast to other GCKs, this activation is mediated solely by the GCK homology region of TNIK. In addition, in Phoenix-A, NIH-3T3, and Hela cells, overexpression of wild type TNIK, but not the kinase mutant form of TNIK, results in the disruption of F-actin structure and the inhibition of cell spreading. Furthermore, TNIK can phosphorylate Gelsolin in vitro. This is the first time that a GCK family kinase is shown to be potentially involved in the regulation of cytoskeleton.