Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Several signal transduction pathways involved in rapidly proliferating cells of the intestine are currently not well understood. In the jejunum, crypt enterocytes are constantly replicating, lower villi are maturing, and upper villi are constantly shed. Type I diabetes is associated with jejunal mucosal hyperplasia, and administration of diflouromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), causes hypoplasia. Phosphorylation of proteins controls cellular proliferation and/or exfoliation. Cell division cycle kinase (p34cdc2) and cyclin B-associated p34cdc2 kinase regulate the cell cycle during the transition from G2-M phase. Our aims were to: 1) investigate the activities of tyrosine kinase, ODC, total p34cdc2 kinase, and cyclin B-associated p34cdc2 kinase and 2) phosphorylate proteins at tyrosine residues in jejunal upper villi, lower villi, and crypt enterocytes of DFMO-treated control and diabetic rats. ⋯ Diabetic jejunal mucosal hyperplasia appears to involve activation of complex signal transduction pathways such as tyrosine kinase, ODC, p34cdc2 kinase, and cyclin B. These enzymes are involved in proliferation and/or exfoliation of jejunal enterocytes. Our results also suggest that tyrosine phosphorylation of a 14 kd protein may be involved in cell exfoliation and that jejunal mucosal hypoplasia may be a synergistic effect caused by down regulation of the above enzymes.