Mobility of the human T lymphocyte surface molecules CD3, CD4, and CD8: regulation by a cAMP-dependent pathway.
The present study was undertaken to determine whether a cAMP pathway mediates the mobility of CD3, CD4, and CD8 within the membrane. Crosslinking CD3, CD4, and CD8 with monoclonal antibody and anti-antibody induced rapid accumulation of intracellular cAMP, occupancy of cAMP receptors, and was temporally associated with the mobilization and directed movement of these molecules to a pole of the cell. This capping process could be partially inhibited in a dose-dependent manner by treatment of T cells with 2',5'-dideoxyadenosine, a ribose-modified adenosine analogue that binds to the P site of the catalytic subunit of adenylate cyclase and reduces adenylate cyclase activity. Furthermore, inhibition of cAMP-dependent endogenous phosphorylation of 17.5-kDa, 23/25-kDa, and 33.5-kDa bands in intact T cells by N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide, a cell-permeable inhibitor of cyclic nucleotide-dependent protein kinase, blocked the capping event. Data support the conclusion that crosslinking of CD3, CD4, and CD8 activates a cAMP-dependent pathway that mediates the mobilization and directed movement of these molecules. cAMP-dependent protein phosphorylation is an integral step leading to the capping process.
Kammer
G M
GM
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Boehm
C A
CA
Rudolph
S A
SA
Schultz
L A
LA
D000067956:Adenylyl Cyclase Inhibitors; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D006801:Humans; D007152:Immunologic Capping; D007546:Isoquinolines / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003839:Deoxyadenosines; D007546:Isoquinolines; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011953:Receptors, Cyclic AMP; D016048:Dideoxyadenosine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D011494:Protein Kinases