Effect of activation of protein kinase C on CD45 isoform expression and CD45 protein tyrosine phosphatase activity in T cells.
The T200/leukocyte common antigen (CD45) is a family of at least five large-molecular weight glycoproteins, which are differentially expressed on T cell subsets. The CD45 antigen consists of a variable heavily glycosylated exterior domain, a single membrane-spanning region, and a large cytoplasmic domain that has protein tyrosine phosphatase (PTPase) activity. In this study, we examined the effects of activation of protein kinase C (PKC) on the phosphorylation and expression of CD45 isoforms and PTPase activity in human T cells. After activation of PKC by phorbol 12-myristate 13-acetate (PMA), CD45RA expression rapidly increased within the first 24 h, whereas CD45R0 expression did not change within this time. However by 48 h, expression of CD45R0 also began to increase. Metabolic labeling showed that the rapid increment in CD45RA expression observed after PMA stimulation is primarily due to increased de novo synthesis of the 205-kDa and not the 220-kDa molecule. PMA treatment resulted in the phosphorylation of each CD45 isoform to a degree corresponding to its relative surface expression. Significantly, we found that the phosphorylation of CD45 by PKC activation down-regulated CD45 PTPase activity.
Yamada
A
A
Division of Tumor Immunology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Streuli
M
M
Saito
H
H
Rothstein
D M
DM
Schlossman
S F
SF
Morimoto
C
C
D000943:Antigens, Differentiation / Q000096:biosynthesis*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006649:Histocompatibility Antigens / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes; D017493:Leukocyte Common Antigens; D008562:Membrane Glycoproteins; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011494:Protein Kinases / Q000235:genetics* / Q000502:physiology; D017027:Protein Tyrosine Phosphatases; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D013755:Tetradecanoylphorbol Acetate