Activation of CD4 T cells by Raf-independent effectors of Ras.
Small GTPase Ras is capable of mediating activation in T lymphocytes by using Raf kinase-dependent signaling pathway. Other effectors of Ras exist, however, suggesting that targets of Ras alternative to Raf may also contribute to T cell functions. Here we demonstrate that Ras(V12G37) mutant that fails to bind Raf, potently increases intracellular calcium concentration and cytokine production in primary antigen-stimulated T cells. From three known effectors which retain the ability to interact with Ras(V12G37), overexpression of phospholipase C epsilon but not that of RIN1 or Ral guanine nucleotide exchange factors enhanced cytokine and nuclear factor-activated T cell reporter T cell responses. Hence T cell activation can be critically regulated by the Ras effector pathway independent from Raf that can be mimicked by phospholipase C epsilon.
Section of Immunobiology, Department of Pathology, and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Jan
J
Czyzyk
Jennifer L
JL
Brogdon
Abdallah
A
Badou
Octavian
O
Henegariu
Paula
P
Preston Hurlburt
Richard
R
Flavell
Kim
K
Bottomly
D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D016133:Polymerase Chain Reaction; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000235:genetics; D020703:ras GTPase-Activating Proteins / Q000276:immunology*
D017931:DNA Primers; D020703:ras GTPase-Activating Proteins; D019908:Proto-Oncogene Proteins c-raf; D010738:Type C Phospholipases