ACTIVATION OF P21(RAS) MAPK SIGNAL-TRANSDUCTION MOLECULES DECREASES WITH AGE IN MITOGEN-STIMULATED T-CELLS FROM RATS/

Signal transduction is ubiquitously involved in the initiation of phys iological signals that lead to growth and proliferation of cells. The signaling cascade mediated by the mitogen-activated protein kinase (MA PK) is considered essential for T cell growth and function. Therefore, it was of interest to determine the influence of age on the induction of MAPK in mitogen-activated T cells. T cells from young (4-6 months) and old (24-26 months) rats responded to concanavalin A (Con A) stimu lation by increasing MAPK, c-jun amino terminal kinase (JNK), and p21( ras) activities. The time course of induction of MAPK/JNK and p21(ras) activities was similar in T cells isolated from young and old rats. T he induction of JNK activity did not change significantly with age; ho wever, the induction of MAPK and p21(ras) activities was significantly less (50 to 65%) in T cells from old rats than in T cells from young rats. Although the relative protein levels of p42 and p44 MAPK did not change with age, the proportion of the phosphorylated p44 MAPK decrea sed with age. In addition, it was found that the in vitro kinase activ ities of the T cell receptor-associated protein tyrosine kinase Lck (p 56(Lck)) and ZAP-70 but not Fyn (p59(Fyn)) were lower in T cells from old rats than in T cells from young rats. The decline in activities of these signaling molecules with age was not associated with changes in their corresponding protein levels. Thus, our results demonstrate tha t aging alters the activation of the signal transduction cascade that leads to T cell activation. (C) 1998 Academic Press.