Differential regulation of proto-oncogenes c-jun and c-fos in T lymphocytes activated through CD28.
The T cell surface molecule CD28 binds to ligands on accessory cells and APCs, playing an important costimulatory role in the response of T cells to Ags. Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete. In addition to activation of phospholipase C gamma 1, ligation of this receptor also seems to activate a calcium-independent, CD28-specific pathway. In this paper, we report that cross-linking of CD28 (but not CD2, CD5, LFA-1, or CD7) leads to an elevation of c-jun mRNA, with only minimal activation of c-fos expression. CD28-dependent induction of c-jun expression requires protein tyrosine kinase activity, but does not depend on activation of a phorbol ester-responsive protein kinase C or elevation of cytosolic calcium. Furthermore, CD28-dependent elevation of c-jun mRNA does not appear to be mediated at the level of mRNA stability. A mechanism is suggested whereby expression of c-jun and junB, in the absence of members of the fos family, can prevent inappropriate activation of T cells caused by ligation of CD28 in the absence of a specific antigenic stimulus.
Chatta
G S
GS
Department of Biochemistry, University of Washington, Seattle 98195.
Spies
A G
AG
Chang
S
S
Mize
G J
GJ
Linsley
P S
PS
Ledbetter
J A
JA
Morris
D R
DR
D001483:Base Sequence; D016227:Benzoquinones; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008213:Lymphocyte Activation / Q000235:genetics; D008969:Molecular Sequence Data; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000235:genetics; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016227:Benzoquinones; D018106:CD28 Antigens; D047029:Lactams, Macrocyclic; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011809:Quinones; D003609:Dactinomycin; D017828:Rifabutin; D004533:Egtazic Acid; D015759:Ionomycin; C020754:herbimycin; D013755:Tetradecanoylphorbol Acetate