V-ABL-MEDIATED APOPTOTIC SUPPRESSION IS ASSOCIATED WITH SHC PHOSPHORYLATION WITHOUT CONCOMITANT MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION

A temperature-sensitive mutant of the v-Abl protein has previously bee n shown to exhibit tyrosine protein kinase activity in Interleukin 3 ( IL-3)-dependent IC.DP cells grown at the permissive temperature (32 de grees C) but not at the restrictive temperature (39 degrees C). These IC.DP cells are dependent on IL-3 for suppression of apoptosis at 39 d egrees C, but at 32 degrees C cells will survive without added growth factor. Both IL-3 and v-Abl stimulated the tyrosine phosphorylation of SHC and GTPase-activating protein. However, while IL-3 stimulated sim ilar levels of tyrosine phosphorylation in p46(shc) and p52(shc), v-Ab l preferentially phosphorylated p52(shc), an event that occurred withi n 1 h of temperature switch. v-Abl also differentially associated with p46(shc) in a temperature-independent manner. In contrast, only IL-3 stimulated detectable increases in both myelin basic protein kinase an d mitogen-activated protein (MAP) kinase kinase in in vitro assays, al though in more specific MAP kinase activity assays a very slight incre ase in the activity of this enzyme was observed after 6 h at the permi ssive temperature. Time course studies suggest that phosphorylation an d association of SHC with v-Abl is insufficient to lead to significant activation of MAP kinase and that activation of the MAP kinase kinase /MAP kinase pathway is not required for apoptotic suppression.