Increased activation of EGF-receptor tyrosine kinase by EGF and TGF-alpha in the colonic mucosa of aged rats.

Freshly isolated colonocytes as well as detergent-solubilized colonic mucosa and lectin purified receptor-enriched mucosal preparations were utilized to compare ligand-induced activation of EGF-receptor (EGF-R) tyrosine kinase (Tyr-k) activity between young (4 months) and aged (24 months) rats. In all three mucosal preparations, EGF and TGF-alpha produced a significantly greater stimulation in EGF-R Tyr-k activity in aged than in young rats, when compared with the corresponding basal levels. This was observed in spite of a significantly higher basal EGF-R Tyr-k activity in the colonic mucosa of aged rats than in young animals. Neither in young nor in aged rats did bombesin cause any significant change in EGF-R Tyr-k activity in the colonic mucosa. In aged rats, TGF-alpha also caused a stimulation in tyrosine phosphorylation of EGF-R and autophosphorylation of the 165 kDa band (a molecular mass that corresponds to EGF-R) and several other mucosal proteins (M, 120, 110, 70, 60, 55 and 50 kDa). We suggest that mitogenic activation of EGF-R Tyr-k may be an important event for the development of hyperproliferative state in the colonic mucosa of aged rats.