Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - v-Abl-mediated apoptotic suppression is associated with SHC phosphorylation without concomitant mitogen-activated protein kinase activation
AU - Owen-Lynch, P J
AU - Wong, A K
AU - Whetton, A D
PY - 1995/3/17
Y1 - 1995/3/17
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.270.11.5956
DO - 10.1074/jbc.270.11.5956
M3 - Journal article
C2 - 7534303
VL - 270
SP - 5956
EP - 5962
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 11
ER -