Home > Research > Publications & Outputs > v-Abl-mediated apoptotic suppression is associa...
View graph of relations

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

Research output: Contribution to Journal/MagazineJournal articlepeer-review

  • P J Owen-Lynch
  • A K Wong
  • A D Whetton
<mark>Journal publication date</mark>17/03/1995
<mark>Journal</mark>Journal of Biological Chemistry
Issue number11
Number of pages7
Pages (from-to)5956-5962
Publication StatusPublished
<mark>Original language</mark>English


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 degrees 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 degrees 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 similar levels of tyrosine phosphorylation in p46shc and p52shc, v-Abl preferentially phosphorylated p52shc, an event that occurred within 1 h of temperature switch. v-Abl also differentially associated with p46shc 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.