STRUCTURAL AND FUNCTIONAL-STUDIES OF THE INTRACELLULAR TYROSINE KINASE MATK GENE AND ITS TRANSLATED PRODUCT
STRUCTURAL AND FUNCTIONAL-STUDIES OF THE INTRACELLULAR TYROSINE KINASE MATK GENE AND ITS TRANSLATED PRODUCT
复制标题
DOI：
10.1074/jbc.270.4.1833
复制
发表时间：
1995-01-27
影响因子：
4.8
通讯作者：
AVRAHAM, H
中科院分区：
文献类型：
--
作者：
AVRAHAM, S;JIANG, SX;AVRAHAM, H
我们最近克隆的cDNA编码一种新的巨核细胞相关的酪氨酸激酶称为MATK。本研究克隆并鉴定了人MATK基因和小鼠MATK cDNA同源物，并对其翻译产物进行了功能研究。人MATK基因由13个外显子和12个内含子组成，编码SH 3和SH 2结构域的遗传单位位于不同的外显子上，推定的ATP结合位点（GXGXXG）位于外显子7上，并且整个催化结构域被细分为7个外显子（7-13），体细胞杂交分析表明，人MATK基因位于19号染色体上，而小鼠Math基因位于10号染色体上，MATK基因5 '侧翼区富含GC序列，并鉴定出几个潜在的顺式作用元件，包括SP 1、加塔-1、APRE和APRE 1。针对MATK mRNA序列的反义寡核苷酸显著抑制巨核祖细胞增殖。功能研究表明，MATK可以磷酸化Src蛋白羧基端保守的酪氨酸，这些结果支持这样的观点，即MATK作为巨核细胞中p60（c-src）的调节剂，并参与调节该谱系细胞生长的途径。
We recently cloned the cDNA which encodes a novel megakaryocyte-associated tyrosine kinase termed MATK. In this study, we have cloned and characterized the human MATK gene as well as the murine homolog of human MATK cDNA and performed functional studies of its translated product, Comparison of the deduced amino acid sequences of human and murine MATK cDNAs revealed 85% homology, indicating that MATK is highly conserved in mouse and human, The human gene consists of 13 exons interrupted by 12 introns, The genetic units which encode the SH3 and SH2 domains are located on separate exons, The putative ATP binding site (GXGXXG) is localized on exon 7, and the entire catalytic domain is subdivided into seven exons (7-13), Somatic cell hybrid analysis indicated that human MATK gene is located on chromosome 19 while the murine Math gene is located on chromosome 10, The immediate 5'-flanking region was highly rich in GC sequences, and potential cis-acting elements were identified including several SP1, GATA-1, APRE, and APRE1, Antisense oligonucleotides directed against MATK mRNA sequences significantly inhibited megakaryocyte progenitor proliferation, Functional studies indicated that MATK can phosphorylate the carboxyl-terminal conserved tyrosine of the Src protein, These results support the notion that MATK acts as a regulator of p60(c-src) in megakaryocytic cells and participates in the pathways regulating growth of cells of this lineage.