Pancreatic reg I binds MKP-1 and regulates cyclin D in pancreatic-derived cells.

Authors: Mueller, CM  Zhang, H  Zenilman, ME 
Citation: Mueller CM, etal., J Surg Res. 2008 Nov;150(1):137-43. doi: 10.1016/j.jss.2008.03.047. Epub 2008 Apr 28.
Pubmed: (View Article at PubMed) PMID:18929742
DOI: Full-text: DOI:10.1016/j.jss.2008.03.047

BACKGROUND: The pancreatic regenerating (reg I) gene and its protein product are derived from acinar cells and are mitogenic to beta- and ductal cells. We studied the mechanism of this mitogenic response. MATERIALS AND METHODS: ARIP (rat ductal) and RIN 1046-38 (rat beta-) cell lines were exposed to exogenous reg I in culture or transfected with a reg I expression vector. Mitogenesis was assessed by MTS assay (CellTiter 96; Promega, Inc., Madison, WI), and cellular mRNA was subjected to gene microarray analysis to determine signal transduction pathways. Yeast two-hybrid technology was then used to determine intracellular binding of reg I protein. RESULTS: Cells exposed to exogenous reg I showed a mitogenic response; cells transfected with reg I expression vector showed inhibited growth. Microarray analysis of the former showed induction of cyclin pathways and mitogen-activated protein kinase phosphatase (MKP-1); cyclins were inhibited in the latter. Northern analysis confirmed gene induction of cyclin D1 and MKP-1; JNK was phosphorylated prior to expression of both. Yeast two-hybrid analysis confirmed a protein-protein interaction with MKP-1; this was confirmed by immunoprecipitation. CONCLUSIONS: Pancreatic-derived cells exposed to reg I grow by activation of signal transduction pathways involving the mitogen-activated protein kinase phosphatases and cyclins, with concomitant induction of MKP-1. However, high intracellular levels of reg I lead to decreased growth, likely via a binding to and inactivation of MKP-1. Inhibition of cell growth, and possible induction of apoptosis, may lead to differentiation of these cells to other cell types.


Gene Ontology Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 10044027
Created: 2015-06-01
Species: All species
Last Modified: 2015-06-01
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.