v-Abl-mediated apoptotic suppression is associated with SHC phosphorylation without concomitant mitogen-activated protein kinase activation

P. J. Owen-Lynch, A. K.Y. Wong, A. D. Whetton

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

A temperature-sensitive mutant of the v-Abl protein has previously been shown to exhibit tyrosine protein kinase activity in Interleukin 3 (IL-3)- dependent IC.DP cells grown at the permissive temperature (32 °C) but not at the restrictive temperature (39 °C). These IC.DP cells are dependent on IL- 3 for suppression of apoptosis at 39 °C, but at 32 °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 similar levels of tyrosine phosphorylation in p46(shc) and p52(shc), v-Abl preferentially phosphorylated p52(shc), an event that occurred within 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 and mitogen-activated protein (MAP) kinase kinase in in vitro assays, although in more specific MAP kinase activity assays a very slight increase in the activity of this enzyme was observed after 6 h at the permissive temperature. Time course studies suggest that phosphorylation and 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.

Original languageEnglish
Pages (from-to)5956-5962
Number of pages7
JournalJournal of Biological Chemistry
Volume270
Issue number11
DOIs
Publication statusPublished - 17 Mar 1995
Externally publishedYes

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