Direct interaction in T-cells between thetaPKC and the tyrosine kinase p59fyn.
The protein kinase C (PKC) family has been clearly implicated in T-cell activation as have several nonreceptor protein-tyrosine kinases associated with the T-cell receptor, including p59fyn. This report demonstrates that thetaPKC and p59fyn specifically interact in vitro, in the yeast two-hybrid system, and in T-cells. Further indications of direct interaction are that p59fyn potentiates thetaPKC catalytic activity and that thetaPKC is a substrate for tyrosine phosphorylation by p59fyn. This interaction may account for the localization of thetaPKC following T-cell activation, pharmacological disruption of which results in specific cell-signaling defects. The demonstration of a physical interaction between a PKC and a protein-tyrosine kinase expands the class of PKC-anchoring proteins (receptors for activated C kinases (RACKs)) and demonstrates a direct connection between these two major T-cell-signaling pathways.
Ron
D
D
Telik, Inc., South San Francisco, California 94080, USA.
Napolitano
E W
EW
Voronova
A
A
Vasquez
N J
NJ
Roberts
D N
DN
Calio
B L
BL
Caothien
R H
RH
Pettiford
S M
SM
Wellik
S
S
Mandac
J B
JB
Kauvar
L M
LM
D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D018274:Electroporation; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D013601:T-Lymphocytes / Q000201:enzymology*
D000906:Antibodies; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta