Beta 1 integrin ligation stimulates tyrosine phosphorylation of phospholipase C gamma 1 and elevates intracellular Ca2+ in pancreatic acinar cells.
We have recently reported increased tyrosine (TYR) phosphorylation of a number of pancreatic acinar cell proteins following antibody ligation of beta 1 integrins (Wrenn and Herman, Biochem, Biophys. Res. Commun. 208, 1995, 978-984). Concurrent with this TYR phosphorylation was a marked activation of protein kinase C (PKC). This led us to investigate phospholipase C gamma 1 (PLC gamma 1), a key enzyme responsible for diacylglycerol generation, as a target for integrin-mediated TYR phosphorylation. Staining with antiphosphotyrosine antibodies revealed increased TYR phosphorylation of immunoprecipitated PLC gamma 1 prepared from beta 1 integrin-ligated acinar cells. Subsequent stripping and reprobing of Western blots with polyclonal anti-PLC gamma 1 was confirmatory. Over this same time period, intracellular [Ca2+] increased from < 100 nM to 600 nM, further suggesting a functional relevance of integrin-linked phosphorylation as a regulatory mechanism in exocrine pancreas.
Wrenn
R W
RW
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912, USA.
Creazzo
T L
TL
Herman
L E
LE
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D019012:Integrin beta1 / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000378:metabolism*; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D010738:Type C Phospholipases / Q000378:metabolism*
D000906:Antibodies; D019012:Integrin beta1; D007527:Isoenzymes; D010750:Phosphoproteins; D019000:Phosphotyrosine; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium