DMBA induces tyrosine phosphorylation of PLC-{gamma}1 and activates the tyrosine kinases lck and fyn in the HPB-ALL human T-cell line
- New Mexico Univ., Albuquerque, NM (United States). Coll. of Pharmacy
Previous studies in this laboratory have demonstrated that DMBA alters biochemical events associated with lymphocyte activation including formation of the second messenger IP{sub 3} and the release of intracellular Ca{sup 2+}. The purpose of the present studies was to evaluate the mechanisms by which DMBA induces IP{sub 3} formation and Ca{sup 2+} release by examining phosphorylation of membrane associated proteins and activation of protein tyrosine kinases lck and fyn. These studies demonstrated that exposure of HPB-ALL cells to 10{mu}M DMBA resulted in a time- and dose-dependent increase in tyrosine phosphorylation of PLC-{gamma}1 that correlated with our earlier findings of IP{sub 3} formation and Ca{sup 2+} release. These results indicate that the effects of DMBA on the PI-PLC signaling pathway are in part, the result of DMBA-induced tyrosine phosphorylation of the PLC-{gamma}1 enzyme. The mechanism of DMBA- induced tyrosine phosphorylation of PLC-{gamma}1 may be due to activation of fyn or lck kinase activity, since it was found that DMBA increased the activity of these PTKs by more than 2-fold. Therefore, these studies demonstrate that DMBA may disrupt T cell activation by stimulating PTK activation with concomitant tyrosine phosphorylation of PLC-{gamma}1, release of IP{sub 3}, and mobilization of intracellular Ca{sup 2+}.
- Research Organization:
- Sandia National Labs., Albuquerque, NM (United States); New Mexico Univ., Albuquerque, NM (United States). Coll. of Pharmacy
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- AC04-76DP00789
- OSTI ID:
- 10136493
- Report Number(s):
- SAND-93-0116C; CONF-930399-1; ON: DE93007603
- Resource Relation:
- Conference: Society of Toxicology meeting,New Orleans, LA (United States),13 Mar 1993; Other Information: PBD: [1993]
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
DIMETHYLBENZANTHRACENE
BIOLOGICAL EFFECTS
PHOSPHOTRANSFERASES
PHOSPHORYLATION
LYMPHOCYTES
INOSINE
ENZYME ACTIVITY
ELECTROPHORESIS
560300
550200
CHEMICALS METABOLISM AND TOXICOLOGY
BIOCHEMISTRY