Distinct expression patterns of ICK/MAK/MOK protein kinases in the intestine implicate functional diversity.
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.
Department of Medicine and Digestive Health Research Center, University of Virginia, Charlottesville, Virginia, United States of America ; Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Tufeng
T
Chen
Di
D
Wu
Christopher A
CA
Moskaluk
Zheng
Z
Fu
D000818:Animals; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*
D000067759:Receptor for Advanced Glycation End Products; C097276:CILK1 protein, human; C000591805:Cilk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C081931:MAK protein, human; C509962:Mak protein, mouse; C498977:Mok protein, mouse; D020928:Mitogen-Activated Protein Kinases