The role of protein kinase C in the regulation of extracellular signal-regulated kinase by the T cell antigen receptor.
The aim of this study was to explore the role of protein kinase C (PKC) in the activation of mitogen-activated protein kinases (MAPK) in T lymphocytes. The MAPK extracellular signal-regulated kinase-2 (ERK2) is activated in response to phorbol esters which stimulate PKC, by transient expression of a constitutively active ras mutant by cell activation via the G protein-coupled type 1 muscarinic acetylcholine receptor (HM1R) or in response to triggering of the T cell antigen receptor (TCR). The relative contribution of PKC to TCR and HM1R regulation of ERK2 was explored by examining the effects of a PKC inhibitor (Ro 31-8425) on ERK2 activation. The data demonstrate that phorbol ester and HM1R regulation of ERK2 was prevented by the PKC inhibitor, but that the inhibitor had no effect on ERK2 activation induced by expression of a constitutively active ras mutant p21v-Ha-ras. Furthermore, the TCR stimulates both PKC and p21ras but TCR regulation of ERK2 was only weakly suppressed by the PKC inhibitor. These data indicate that PKC has a potential but not a predominant role in TCR regulation of ERK2.
Izquierdo
M
M
Lymphocyte Activation Laboratory, ICRF Laboratories, Lincoln's Inn Fields, London.
Leevers
S J
SJ
Williams
D H
DH
Marshall
C J
CJ
Weiss
A
A
Cantrell
D
D
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006150:Guanine Nucleotides / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction
D006150:Guanine Nucleotides; D007211:Indoles; D008301:Maleimides; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011976:Receptors, Muscarinic; C071924:Ro 31-8425; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1