Regulation of pancreatic tyrosine kinase and phosphatase activities by cholecystokinin and somatostatin
Rivard, N.; Lebel, D.; Lainé, J.; Morisset, J.
American Journal of Physiology 266(6 Pt 1): G1130-G1138
1994
ISSN/ISBN: 0002-9513 PMID: 7912895 Document Number: 435233
Phosphorylation and dephosphorylation of proteins on tyrosyl residues are important reactions involved in cellular activities, namely, those associated with growth and differentiation. Although it is accepted that cholecystokinin (CCK) and somatostatin (SS) stimulate and inhibit pancreatic growth and secretion, the cellular mechanisms by which these two hormones trigger their stimulatory and inhibitory effects are not well known. It has recently been suggested that, in acinar cells, one of the early signals of SS would involve activation of a membrane tyrosine phosphatase, whereas the signal associated with CCK may involve stimulation of protein tyrosine phosphorylation. This study examines the effects of caerulein (Cae) and SMS-201-995 (SMS) on pancreatic growth, particulate and crude cytosolic tyrosine kinase (TRK), and phosphotyrosine phosphatase (PTase) activities. Rats infused intravenously with 0.05% bovine serum albumin (control), Cae (0.25 mu-g cntdot kg-1 cntdot h-1), or SMS (5 mu-g cntdot kg-1 cntdot h-1) were killed after 0.5, 1, 2, 3, 4, 8, 12, 24, and 48 h of infusion. The pancreas was excised, weighed, and evaluated for contents of DNA and protein and for TRK and PTase activities. The effects of subtotal pancreatectomy on TRK and PTase activities were also examined after 1, 2, 3, 4, and 7 days. In response to Cae, pancreatic growth was evident after 48 h and was accompanied by sustained increases in particulate TRK and particulate PTase. Increases in membrane PTase activities were localized on membranes of the zymogen granules. SMS treatment was associated with increases in pancreatic weight and protein as a result of inhibition of secretion. Particulate and crude cytosolic PTase activities were transiently increased during the 1st h of SMS infusion, whereas particulate and crude cytosolic TRK activities were concomitantly reduced. SMS significantly stimulated basal particulate PTase activity during the first 2 h of its infusion without any effect on the zymogen granule membrane. Pancreatectomy strongly stimulated particulate and crude cytosolic TRK with transient decreases in particulate and crude cytosolic PTase. Activation of TRK may be an important step in the growth-promoting effect of caerulein and pancreatectomy; the caerulein-associated increase in particulate PTase activity seems to be related to protein secretion. The transient effect of SMS on PTase activity may suggest a role in the early events associated with negative control of proliferation.