skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: DMBA induces tyrosine phosphorylation of PLC-[gamma]1 and activates the tyrosine kinases lck and fyn in the HPB-ALL human T-cell line

Abstract

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+].

Authors:
; ; ;  [1]
  1. New Mexico Univ., Albuquerque, NM (United States). Coll. of Pharmacy
Publication Date:
Research Org.:
Sandia National Labs., Albuquerque, NM (United States); New Mexico Univ., Albuquerque, NM (United States). Coll. of Pharmacy
Sponsoring Org.:
USDOE; USDOE, Washington, DC (United States)
OSTI Identifier:
6711987
Report Number(s):
SAND-93-0116C; CONF-930399-1
ON: DE93007603
DOE Contract Number:  
AC04-76DP00789
Resource Type:
Conference
Resource Relation:
Conference: Society of Toxicology meeting, New Orleans, LA (United States), 13 Mar 1993
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; DIMETHYLBENZANTHRACENE; BIOLOGICAL EFFECTS; PHOSPHOTRANSFERASES; PHOSPHORYLATION; ELECTROPHORESIS; ENZYME ACTIVITY; INOSINE; LYMPHOCYTES; ANIMAL CELLS; AROMATICS; AZAARENES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CHEMICAL REACTIONS; CONDENSED AROMATICS; CONNECTIVE TISSUE CELLS; ENZYMES; HETEROCYCLIC COMPOUNDS; LEUKOCYTES; MATERIALS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PHOSPHORUS-GROUP TRANSFERASES; PROTEINS; PURINES; RIBOSIDES; SOMATIC CELLS; TRANSFERASES; 560300* - Chemicals Metabolism & Toxicology; 550200 - Biochemistry

Citation Formats

Archuleta, M M, Schieven, G L, Ledbetter, J A, and Burchiel, S W. DMBA induces tyrosine phosphorylation of PLC-[gamma]1 and activates the tyrosine kinases lck and fyn in the HPB-ALL human T-cell line. United States: N. p., 1993. Web.
Archuleta, M M, Schieven, G L, Ledbetter, J A, & Burchiel, S W. DMBA induces tyrosine phosphorylation of PLC-[gamma]1 and activates the tyrosine kinases lck and fyn in the HPB-ALL human T-cell line. United States.
Archuleta, M M, Schieven, G L, Ledbetter, J A, and Burchiel, S W. 1993. "DMBA induces tyrosine phosphorylation of PLC-[gamma]1 and activates the tyrosine kinases lck and fyn in the HPB-ALL human T-cell line". United States.
@article{osti_6711987,
title = {DMBA induces tyrosine phosphorylation of PLC-[gamma]1 and activates the tyrosine kinases lck and fyn in the HPB-ALL human T-cell line},
author = {Archuleta, M M and Schieven, G L and Ledbetter, J A and Burchiel, S W},
abstractNote = {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+].},
doi = {},
url = {https://www.osti.gov/biblio/6711987}, journal = {},
number = ,
volume = ,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 1993},
month = {Fri Jan 01 00:00:00 EST 1993}
}

Conference:
Other availability
Please see Document Availability for additional information on obtaining the full-text document. Library patrons may search WorldCat to identify libraries that hold this conference proceeding.

Save / Share: