A receptor that subserves reovirus binding can inhibit lymphocyte proliferation triggered by mitogenic signals.
A novel surface receptor complex involved in inhibition of T-cell proliferation is described. Biochemical isolation revealed two non-covalently associated proteins of about M(r) 65,000 (p65) and 95,000 (p95). These polypeptides may be related. The p65 form is expressed after cellular activation and replication and is recognized by monoclonal antibody (mAb) 87.92.6 or reovirus hemagglutinin as unnatural ligands. The p95 species is associated with tyrosine kinase enzymatic activity. Receptor ligation results in rapid alteration of the phosphotyrosine content of cellular substrates, and this activity correlates with antiproliferative effects. The inhibition of proliferation is a time-dependent reversible arrest at the G1-S phase of the cell cycle. Activation through the T-cell receptor, protein kinase C, or addition of cytokines does not reverse the antiproliferative effect. This receptor complex may define novel features of T-cell proliferation.
Saragovi
H U
HU
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Bhandoola
A
A
Lemercier
M M
MM
Akbar
G K
GK
Greene
M I
MI
D000818:Animals; D000911:Antibodies, Monoclonal; D016193:G1 Phase; D006389:Hemagglutinins, Viral / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008934:Mitogens / Q000494:pharmacology; D008970:Molecular Weight; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D012087:Reoviridae / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D006389:Hemagglutinins, Viral; D008934:Mitogens; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011505:Protein-Tyrosine Kinases