ras protein activity is essential for T-cell antigen receptor signal transduction.
In a Jurkat cell model of T-cell activation an interleukin-2 promoter/reporter gene construct was activated by antigen receptor agonism in combination with the lymphokine interleukin-1. Antigen receptor signals could be mimicked by suboptimal activation of protein kinase C (PKC) with phorbol esters in combination with calcium mobilization by an ionophore. In cotransfection experiments, oncogenic rats obviated the need for PKC stimulation but did not replace either the calcium signal or interleukin-1. Activated ras expression also replaced the requirement for PKC stimulation in activation of the T-cell transcription factor NF-AT. A dominant inhibitory ras mutant specifically blocked antigen receptor agonism, indicating that ras activity is required for antigen receptor signaling. In addition, an inhibitor of PKC blocked both activated ras and phorbol ester stimulation, suggesting a role for ras upstream of PKC.
Baldari
C T
CT
Department of Evolutionary Biology, University of Siena, Italy.
Heguy
A
A
Telford
J L
JL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004268:DNA-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D005799:Genes, Dominant; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology; D008213:Lymphocyte Activation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D007546:Isoquinolines; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010879:Piperazines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D013755:Tetradecanoylphorbol Acetate