Identification of calcineurin regulated phosphorylation sites on CRHSP-24.
CRHSP-24 is a prominently regulated phosphoprotein in pancreatic acinar cells where it is the major substrate for the serine/threonine protein phosphatase, calcineurin, in response to secretagogues. We now identify the four regulated sites of CRHSP-24 phosphorylation as serines 30, 32, 41, and 52 and show that Ser(30) and Ser(32) are directly dephosphorylated by calcineurin. Coordinate phosphorylation/dephosphorylation of these four serines explains the multiple phosphorylated isoforms of CRHSP-24 present in acinar cells and provides a molecular framework to study CRHSP-24 regulation by secretagogues and growth factor-induced kinases and phosphatases in vivo.
Lee
SaeHong
S
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Wishart
Matthew J
MJ
Williams
John A
JA
D000595:Amino Acid Sequence; D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010179:Pancreas / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C513278:Carhsp1 protein, rat; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D012694:Serine; D019703:Calcineurin