Research output: Contribution to Journal/Magazine › Journal article › peer-review
<mark>Journal publication date</mark> | 25/07/1993 |
---|---|
<mark>Journal</mark> | Journal of Biological Chemistry |
Issue number | 21 |
Volume | 268 |
Number of pages | 8 |
Pages (from-to) | 15696-15703 |
Publication Status | Published |
<mark>Original language</mark> | English |
A temperature-sensitive mutant of the v-abl oncoprotein has previously been shown to have markedly reduced tyrosine protein kinase activity in interleukin 3 (IL-3)-dependent cells grown at restrictive (39-degrees-C), compared to permissive (32-degrees-C) temperatures. Transfection of this mutant v-abl into the IC2.9 cell line, generated the IC.DP subclone which was dependent on IL-3 for survival at 39-degrees-C, but not at 32-degrees-C. Furthermore, IC.DP cells cultured at 32-degrees-C exhibited IL-3-independent thymidine incorporation, which was not apparent at 39-degrees-C. Switching cells from the restrictive to the permissive temperature resulted in an increase in cellular inositol-1,4,5-trisphosphate, choline phosphate and diacylglycerol levels in the IC.DP cell line. These increases were only observed after a lag period of 4 h. Within 2 h of switching IC.DP cells previously maintained at 32 to 39-degrees-C, there was a significant decrease in all three metabolites. Temperature switches had no effect upon these metabolites in the parent IC2.9 cell line. Down-regulation of protein kinase C inhibited v-abl-stimulated DNA synthesis in IC.DP cells cultured at 32-degrees-C. IC.DP cells cultured at 32-degrees-C were found to have a constitutively activated Na+/H+ antiport, although this activation was inhibited by the down-modulation of protein kinase C. These data indicate a role for phospholipid hydrolysis and protein kinase C activation in V-ABL-mediated abrogation of IL-3 dependence.