RIBOSOMAL-PROTEIN S6 KINASE AND PROTEIN-KINASE-C ACTIVATION BY EPIDERMAL GROWTH-FACTOR AFTER TEMPORARY RENAL ISCHEMIA

An initial event in cell response to growth factors is the change in t he state of phosphorylation of a number of cellular proteins playing a role in cell proliferation. The effects of a single dose of exogenous ly administered epidermal growth factor (EGF) on renal serine/threonin e protein kinases such as ribosomal protein S6 kinase(s) and protein k inase C (PKC) and on [H-3]thymidine incorporation into tubule cell nuc lei have been studied during the regenerative repair response after te mporary renal ischemia in the rat, followed by reperfusion for up to 7 2 h. During the postischemic reflow, the PKC and S6 kinase activities increased at 24 and 72 h, respectively. EGF anticipated both increases : the PKC at 4 and the S6 kinase(s) at 24 h. Associated with this EGF- induced rise of S6 kinase activity, a significant increase in renal tu bule cell proliferation was observed. These studies suggest the presen ce of a growth factor-activated serine/threonine threonine phosphoryla tion cascade in the rat kidney participating in the regulation of cell growth during recovery from an ischemic insult.