Regulation of expression of CD27, a T cell-specific member of a novel family of membrane receptors.
CD27 belongs to a newly defined family of transmembrane R, including the nerve growth factor R, two distinct TNF R and CD40. The function of CD27 is unknown, but on the basis of structural and functional properties, we postulate that it plays a role in the events subsequent to T cell activation, possibly as a cytokine R. We have analyzed the mechanisms underlying the regulation of CD27 protein expression. Membrane expression of CD27 strongly increases after T cell activation via the TCR/CD3 complex or the CD2 molecule. In contrast, direct stimulation of protein kinase C by phorbol esters markedly down-regulates CD27 surface expression. This down-regulation most likely does not result from CD27 phosphorylation, because both anti-CD3 mAb and PMA induce hyperphosphorylation of CD27 on serine residues. Rather, membrane expression seems to be regulated primarily at the RNA level. Stimulation of T cells with anti-CD3 mAb strongly increases steady state CD27 mRNA levels, whereas PMA treatment greatly reduces these transcript levels. Dissection of the TCR/CD3-induced signaling pathways showed that cytoplasmic cAMP as well as Ca2+ concentrations contribute to the increase of CD27 expression. These data indicate that upon Ag-specific T cell stimulation, membrane expression of CD27 is regulated at the RNA level through the joint action of distinct TCR/CD3-associated signaling pathways.
de Jong
R
R
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Loenen
W A
WA
Brouwer
M
M
van Emmerik
L
L
de Vries
E F
EF
Borst
J
J
van Lier
R A
RA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics*; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002455:Cell Division; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000096:biosynthesis; D012313:RNA / Q000032:analysis / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D010835:Phytohemagglutinins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D005576:Colforsin; D012313:RNA; D003994:Bucladesine; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium