title: D1 and D2 dopamine receptor-mediated inhibition of activated normal T cell proliferation is lost in jurkat T leukemic cells.
abstract: Dopamine is a catecholamine neurotransmitter, which plays an important role in the regulation of T cell functions. In activated T cells from normal volunteers, stimulation of D(1) and D(2) dopamine receptors inhibit cell proliferation and cytokine secretion. However, there is no report yet regarding the regulatory role of D(1) and D(2) dopamine receptors in abnormally proliferating T cells. The present study investigates the expression and effect of activation of these dopamine receptors in Jurkat cells, a leukemic T cell line showing uncontrolled proliferation. Like normal human T cells, in Jurkat cells, D(1) and D(2) dopamine receptors are also expressed; however, unlike activated normal T cells, stimulation of these dopamine receptors in Jurkat cells fails to inhibit their T cell receptor-induced proliferation. This alteration is due to failure of D(1) dopamine receptor-mediated activation of cyclic AMP signaling and a missense mutation at the third cytoplasmic loop of D(2) dopamine receptors affecting inhibition of phosphorylation of ZAP-70, an important downstream protein transducing signal from the T cell receptor. These results help to understand the biology of abnormal proliferation of T cells in pathophysiological conditions where dopamine plays an important role.
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Biswarup
authors.initials: B
authors.lastname: Basu
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio 43210.
authors.forename: Chandrani
authors.initials: C
authors.lastname: Sarkar
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio 43210.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Chakroborty
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Subhalakshmi
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Saurav
authors.initials: S
authors.lastname: Shome
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata 700026, India. Electronic address: partha42002@yahoo.com.
authors.forename: Partha Sarathi
authors.initials: PS
authors.lastname: Dasgupta
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio 43210; Arthur G. James Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210. Electronic address: sujit.basu@osumc.edu.
authors.forename: Sujit
authors.initials: S
authors.lastname: Basu
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D004298:Dopamine