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 FGF-receptor (EGF-R) tyrosine kinase (Tyr-k) activity between young (4 months) and aged (2 4 months) rats. In all three mucosal preparations, EGF and TGF-alpha p roduced a significantly greater stimulation in EGF-R Tyr-k activity in aged than in young rats, when compared with the corresponding basal l evels. 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 anim als. Neither in young nor in aged rats did bombesin cause any signific ant change in EGF-R Tyr-k activity in the colonic mucosa. In aged rats , TGF-alpha also caused a stimulation in tyrosine phosphorylation of E GF-R and autophosphorylation of the 165 kDa band (a molecular mass tha t corresponds to EGF-R) and several other mucosal proteins (M(r), 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 hyperprol iferative state in the colonic mucosa of aged rats.