Activation of SH2-containing proteins by insulin in proliferating mouse parotid gland acinar cells.
Chronic treatment of mice with insulin results in hypertrophy and hyperplasia of the parotid and submandibular glands (Wang et al.: 1994, Proc Soc Exp Biol Med 205:353-361). Hyperplasia of the parotid gland is mediated by the elevation of tyrosine phosphorylation of phospholipase C gamma, p21ras-GTPase activating protein (p21ras-GAP) and phosphatidylinositol 3-kinase. These proteins were found to be associated with the insulin receptor substrate-1 most likely through src homology (SH2) domains of these proteins. There was also a transient increase in intracellular cAMP and protein kinase A during the first day of treatment which declined by Day 3 to near control values. Protein kinase C activity, on the other hand, remained elevated for the 3-day injection regimen. Thus, acinar cell proliferation induced by insulin requires activation of many of the same signaling components as other tyrosine kinase possessing growth factor receptors.
Wang
P L
PL
Department of Oral Biology, University of Florida, Gainesville 32610.
Purushotham
K R
KR
Humphreys-Beher
M G
MG
D000818:Animals; D002455:Cell Division; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis; D020690:GTPase-Activating Proteins; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D020690:GTPase-Activating Proteins; D007328:Insulin; D011506:Proteins; D014443:Tyrosine; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases