Gastric mucosal tyrosine kinase activity during aging and its relationship to cell proliferation in rats

The relationship between tyrosine kinase activity and cellular proliferative activity was investigated in the gastric mucosa. For the purpose of comparison, the liver and the pancreas were also included. Groups of 2-, 14- and 22-month-old male Fischer-344 rats were used. Tyrosine kinase activity was determined in the membrane fraction (30,000 x g pellet) utilizing a synthetic polymer, Glu-Tyr (4:1), as substrate. Cellular proliferative activity was assessed by measuring ornithine decarboxylase in the 20,000 x g supernatant. In all age groups, gastric mucosal tyrosine kinase activity was found to be 10-20-fold higher than in the liver or pancreas. In addition, gastric mucosal tyrosine kinase activity in 22-month-old rats was 35-70% higher than in their 2- and 14-month-old counterparts. Gastric mucosal ornithine decarboxylase activity also followed essentially the same pattern as that of tyrosine kinase in that the highest activity was observed in 22-month-old rats. Increased gastric mucosal proliferative activity in 22-month-old rats was also associated with increased tyrosine-phosphorylation of a mucosal membrane protein with an apparent Mr of 53,000. An opposite phenomenon occurred in the pancreas whose proliferative activity was found to be the lowest. It is concluded that the age-associated changes in gastric mucosal proliferative activity are accompanied by parallel alterations in tyrosine kinase activity. Tyrosine-phosphorylation of a 53 kDa membrane protein may play a role in the regulation of cell proliferation.