v-Abl protein tyrosine kinase (PTK) mediated suppression of apoptosis is associated with the up-regulation of Bcl-XL.
We demonstrated previously that the activation of v-Abl protein tyrosine kinase (PTK) in IC.DP murine pre-mast cells resulted in suppression of apoptosis after withdrawal of interleukin 3 (IL-3), that protein kinase C (PKC) translocated to the nucleus 6 h after v-Abl PTK activation and that inhibition of PKC restored apoptosis after IL-3 deprivation in the presence of v-Abl PTK activity. Here we demonstrate that v-Abl PTK activation is followed by an approximately twofold increase in mRNA level of Bcl-XL by 6 h and a corresponding increase in Bcl-XL protein level by 24 h. Bcl-xL RNA and protein decreased in IL-3 deprived cells in the absence of v-Abl PTK activity. Exposure of cells with v-Abl PTK active to the PKC inhbitor calphostin C (125 ng/ml) prevented the increase in Bcl-xL protein and resulted in apoptosis. No changes in Bax or Bcl-2 protein level were noted after IL-3 withdrawal and/or activation of v-Abl PTK. Bak was barely detectable and Bad protein level decreased in cells undergoing apoptosis. The data suggest that suppression of apoptosis by v-Abl PTK in the absence of IL-3 is associated with PKC signalling and the upregulation of Bcl-xL in IC.DP cells.
Chen
Q
Q
Molecular Pharmacology Group, School of Biological Sciences, Manchester University, UK.
Turner
J
J
Watson
A J
AJ
Dive
C
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D005434:Flow Cytometry; D007377:Interleukin-3 / Q000172:deficiency; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D007377:Interleukin-3; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl