Glucose stimulates the association of Crk with p130Cas in pancreatic beta cells.
OBJECTIVE
Previously, we demonstrated glucose-induced beta-cell tyrosine phosphorylation of p130Cas, a protein containing 15 YXXP repeats that can become tyrosine phosphorylated and bind Src-homology 2 (SH2)-containing proteins. In light of the importance of p130Cas in other cell types, we determined which beta-cell proteins exhibited glucose-induced association with p130Cas.


METHODS
beta cells were stimulated with glucose and/or the muscarinic agonist carbachol to determine which SH2-containing adapter proteins underwent glucose-induced association with p130Cas.


RESULTS
The SH2-containing adapter protein Crk underwent glucose-induced association with p130Cas, while other SH2-containing proteins such as grb2, PI3 kinase, Shp-2, paxillin, and pyk2 did not. Glucose-induced Crk-p130Cas association was rapid and sustained and was maximal with the combination of glucose and carbachol, paralleling insulin secretion. There was no increased tyrosine phosphorylation of Crk itself. The expression of Crk in isolated rat islets was also demonstrated.


CONCLUSIONS
beta cells contain the SH2-containing adapter protein Crk, which undergoes glucose-induced association with p130Cas.
Lee
Thomas N
TN
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Gold
Gerald
G
Workman
Robert
R
Cook
Carolyn A
CA
Konrad
Robert J
RJ
D000818:Animals; D002460:Cell Line; D050719:Crk-Associated Substrate Protein; D005947:Glucose / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk; D051381:Rats; D017207:Rats, Sprague-Dawley; D050717:Retinoblastoma-Like Protein p130
C493843:Bcar1 protein, rat; C493872:Crk protein, rat; D050719:Crk-Associated Substrate Protein; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D050717:Retinoblastoma-Like Protein p130; D005947:Glucose