Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulatory protein kinases are involved in various cellular processes such as proliferation, differentiation, and apoptosis. Using cDNA differential display, we identified MOK, a member of the mitogen-activated protein kinase superfamily, as one of the genes induced by a caudal-related homeobox transcription factor, Cdx2. Analysis of the 5'-flanking region of the MOK gene led to the identification of primary Cdx2 responsive element, and an electrophoretic mobility shift assay indicated that Cdx2 binds to that element. The interaction of Cdx2 with the MOK promoter region was further confirmed in vivo by chromatin immunoprecipitation assays. The expression of MOK mRNA and protein was limited to the crypt epithelial cells of the mouse intestine. We also determined the MOK activity associated with the growth arrest and induction of differentiation by sodium butyrate or Cdx2 expression in the human colon cancer cell line HT-29. Taken together, these data indicate that MOK is a direct target gene for Cdx2, and that MOK may be involved in growth arrest and differentiation in the intestinal epithelium.
 ...
PMID:Cdx2 homeodomain protein regulates the expression of MOK, a member of the mitogen-activated protein kinase superfamily, in the intestinal epithelial cells. 1532 90

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.
...
PMID:Distinct expression patterns of ICK/MAK/MOK protein kinases in the intestine implicate functional diversity. 2424 86