Distinct expression patterns of ICK/MAK/MOK protein kinases in the intestine implicate functional diversity.
Distinct expression patterns of ICK/MAK/MOK protein kinases in the intestine implicate functional diversity.
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DOI：
10.1371/journal.pone.0079359
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fu Z
中科院分区：
文献类型：
--
作者：
Chen T;Wu D;Moskaluk CA;Fu Z
ICK/MRK（肠细胞激酶/MAK相关激酶）、MAK（雄性生殖细胞相关激酶）和MOK（MAPK/MAK/MRK重叠激酶）是蛋白激酶组中密切相关的丝氨酸/苏氨酸蛋白激酶。ICK/MAK/MOK家族的生物学功能和调节机制仍然很难理解。尽管它们的催化结构域具有显着相似性，但它们在C末端非催化结构域的序列和结构组织上显着不同，这引发了它们是否具有不同、重叠或冗余的生物功能的问题。为了深入了解它们的生物学活性并为功能研究奠定基础，我们研究了ICK/MAK/MOK蛋白激酶在肠道中的时空分布模式和表达动态。我们发现，ICK/MAK/MOK蛋白显示不同的表达模式沿着结肠轴和在出生后的小鼠发育。此外，它们在肠上皮细胞和间充质细胞之间有差异分配。在人原发性结肠癌标本中，ICK蛋白水平显著增加，但MAK蛋白水平没有显著增加。与正常肠粘膜相比，小鼠肠腺瘤中ICK蛋白表达上调，而MOK蛋白表达下调。这些数据表明ICK/MAK/MOK蛋白激酶在调节肠肿瘤中的不同作用。两者合计，我们的研究结果表明，ICK/MAK/MOK蛋白在肠道中的表达可以差异和动态调节，暗示这组蛋白激酶内的显着的功能多样性。
ICK/MRK (intestinal cell kinase/MAK-related kinase), MAK (male germ cell-associated kinase), and MOK (MAPK/MAK/MRK-overlapping kinase) are closely related serine/threonine protein kinases in the protein kinome. The biological functions and regulatory mechanisms of the ICK/MAK/MOK family are still largely elusive. Despite significant similarities in their catalytic domains, they diverge markedly in the sequence and structural organization of their C-terminal non-catalytic domains, raising the question as to whether they have distinct, overlapping, or redundant biological functions. In order to gain insights into their biological activities and lay a fundamental groundwork for functional studies, we investigated the spatio-temporal distribution patterns and the expression dynamics of ICK/MAK/MOK protein kinases in the intestine. We found that ICK/MAK/MOK proteins display divergent expression patterns along the duodenum-to-colon axis and during postnatal murine development. Furthermore, they are differentially partitioned between intestinal epithelium and mesenchyme. A significant increase in the protein level of ICK, but not MAK, was induced in human primary colon cancer specimens. ICK protein level was up-regulated whereas MOK protein level was down-regulated in mouse intestinal adenomas as compared with their adjacent normal intestinal mucosa. These data suggest distinct roles for ICK/MAK/MOK protein kinases in the regulation of intestinal neoplasia. Taken together, our findings demonstrate that the expressions of ICK/MAK/MOK proteins in the intestinal tract can be differentially and dynamically regulated, implicating a significant functional diversity within this group of protein kinases.
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影响因子：
30.8
作者：
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