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PMID: 2829202 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mobility of the human T lymphocyte surface molecules CD3, CD4, and CD8: regulation by a cAMP-dependent pathway.

Kammer GM, Boehm CA, Rudolph SA, Schultz LA

Abstract

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.

MeSH Terms
Adenylyl Cyclase Inhibitors Antibodies, Monoclonal/immunology Antigens, Differentiation, T-Lymphocyte/immunology,metabolism Cyclic AMP/physiology Deoxyadenosines/analogs & derivatives,pharmacology Dideoxyadenosine/analogs & derivatives Humans Immunologic Capping Isoquinolines/pharmacology Membrane Proteins/metabolism Phosphorylation Protein Kinase Inhibitors Protein Kinases/metabolism Receptors, Cyclic AMP/metabolism T-Lymphocytes/metabolism
Chemicals
Adenylyl Cyclase Inhibitors Antibodies, Monoclonal Antigens, Differentiation, T-Lymphocyte Deoxyadenosines Isoquinolines Membrane Proteins Protein Kinase Inhibitors Receptors, Cyclic AMP Dideoxyadenosine N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide 2',5'-dideoxyadenosine Cyclic AMP Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kammer G M
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
Boehm C A
Rudolph S A
Schultz L A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1988-02-00
Pages
792-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC279641
Subset
IM
Grants
NIADDK NIH HHS · AM-07505 · United States
NIADDK NIH HHS · AM-33072 · United States
NCRR NIH HHS · M01-RR00080 · United States
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