Raf-1 provides a dominant but not exclusive signal for the induction of CD69 expression on T cells

Eur J Immunol. 1995 Dec;25(12):3215-21. doi: 10.1002/eji.1830251203.


Stimulation of the T cell antigen receptor (TCR) induces a number of intracellular signaling pathways which lead to the transcription of a variety of new genes. Of the newly synthesized proteins, the earliest to be detected on the cell surface is the type II integral membrane protein CD69. Cross-linking of this activation antigen induces signaling events related to T cell activation. The proto-oncogene product Ras has been reported to up-regulate CD69. However, which of the potential effectors of Ras induces the expression of CD69 has remained unclear. Using transient transfection, we have shown a constitutively active form of the serine/threonine kinase Raf-1 to be sufficient to induce CD69 expression in human Jurkat T cells. Raf-1 was further shown to be necessary for PMA-induced CD69 expression, since transfection of a dominant inhibitory form of Raf-1 blocked the up-regulation of CD69 by PMA. In addition, studies with the calcium ionophore ionomycin identified a previously uncharacterized pathway regulating the expression of CD69 in T cells. Elevation of intracellular calcium induced the expression of CD69 in both Jurkat cells and peripheral blood T cells. This effect was sensitive to the immunosuppressive drug cyclosporin A, indicating that calcium-induced CD69 expression is mediated by the protein phosphatase calcineurin. Taken together, these results define Raf-1 as the major signaling mediator of CD69 expression in T cells and suggest that multiple mechanisms exist to regulate the level of CD69 expression following TCR stimulation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, CD / biosynthesis*
  • Antigens, CD / drug effects*
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis*
  • Antigens, Differentiation, T-Lymphocyte / drug effects*
  • Cyclosporine / pharmacology
  • Dose-Response Relationship, Immunologic
  • Down-Regulation / drug effects
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Lectins, C-Type
  • Lymphoma
  • Mitogens / pharmacology
  • Protein Serine-Threonine Kinases / pharmacology*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / pharmacology*
  • Proto-Oncogene Proteins c-raf
  • Signal Transduction / drug effects*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Immunosuppressive Agents
  • Ionophores
  • Lectins, C-Type
  • MAS1 protein, human
  • Mitogens
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Ionomycin
  • Cyclosporine
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Tetradecanoylphorbol Acetate