Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin
Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin
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DOI：
10.1016/s0006-291x(02)02718-3
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发表时间：
2002-12-20
影响因子：
3.1
通讯作者：
Dahlbäck, B
中科院分区：
文献类型：
--
作者：
Hafizi, S;Alindri, F;Dahlbäck, B
Ax 1受体酪氨酸激酶与几种恶性肿瘤有关，是维生素K依赖性生长因子Gas 6的受体。从酵母双杂交筛选蛋白质-蛋白质相互作用的Ax 1胞质结构域，我们检测到一个以前未表征的SH 2结构域的蛋白质。我们克隆了两种新的剪接变体，产生1409-和1419-氨基酸的蛋白质，不同的只是在它们的N-末端残基，并产生一个150 kDa的蛋白质产物，通过体外翻译。Ax 1相互作用的C-末端包含一个串联的SH 2和PTB结构域组合同源的粘着斑蛋白张力蛋白。通过免疫共沉淀和双杂交分析，我们检测了Ax 1与哺乳动物细胞中两个结构域的相互作用。此外，该蛋白具有一个N-末端的佛波酯结合C1结构域以及中央酪氨酸磷酸酶基序。因此，我们将含有C1结构域的蛋白质命名为磷酸酶和TENSin同源物（C1-TEN）。人组织中C1-TEN的北方印迹分析显示在心脏、肾脏和肝脏中表达最高。总之，我们已经确定了一种新的多结构域的细胞内蛋白，与Ax 1相互作用，并可能进一步参与其他信号转导途径。(C)2002 Elsevier Science（美国）。All rights reserved.
Ax1 receptor tyrosine kinase is implicated in several malignancies and is the receptor for the vitamin K-dependent growth factor Gas6. From a yeast two-hybrid screen of protein-protein interactions with the Ax1 cytoplasmic domain, we detected a previously uncharacterised SH2 domain-containing protein. We cloned two novel splice variants of this protein that give rise to 1409- and 1419-amino acid proteins, differing only in their N-terminal residues and yielding a 150-kDa protein product by in vitro translation. The Ax1-interacting C-terminus contains a tandem SH2 and PTB domain combination homologous to the focal adhesion protein tensin. We detected interaction of Ax1 with both domains in mammalian cells by co-immunoprecipitation and two-hybrid analyses. In addition, the protein possesses an N-terminal putative phorbol ester-binding C1 domain as well as a central tyrosine phosphatase motif. Thus, we have named the protein C1 domain-containing phosphatase and TENsin homologue (C1-TEN). Northern blot analysis of C1-TEN in human tissues revealed highest expression in heart, kidney, and liver. In summary, we have identified a novel multi-domain intracellular protein that interacts with Ax1 and which may furthermore be involved in other signal transduction pathways. (C) 2002 Elsevier Science (USA). All rights reserved.