Differential function of PTPalpha and PTPalpha Y789F in T cells and regulation of PTPalpha phosphorylation at Tyr-789 by CD45.
CD45 is a major membrane protein tyrosine phosphatase (PTP) expressed in T cells where it regulates the activity of Lck, a Src family kinase important for T cell receptor-mediated activation. PTPalpha is a more widely expressed transmembrane PTP that has been shown to regulate the Src family kinases, Src and Fyn, and is also present in T cells. Here, PTPalpha was phosphorylated at Tyr-789 in CD45(-) T cells but not in CD45(+) T cells suggesting that CD45 could regulate the phosphorylation of PTPalpha at this site. Furthermore, CD45 could directly dephosphorylate PTPalpha in vitro. Expression of PTPalpha and PTPalpha-Y789F in T cells revealed that the mutant had a reduced ability to decrease Fyn and Cbp phosphorylation, to regulate the kinase activity of Fyn, and to restore T cell receptor-induced signaling events when compared with PTPalpha. Conversely, this mutant had an increased ability to prevent Pyk2 phosphorylation and CD44-mediated cell spreading when compared with PTPalpha. These data demonstrate distinct activities of PTPalpha and PTPalpha-Y789F in T cells and identify CD45 as a regulator of PTPalpha phosphorylation at tyrosine 789 in T cells.
Maksumova
Lola
L
Departments of Pediatrics, Microbiology and Immunology, and Pathology and Laboratory Medicine, University of British Columbia and Child & Family Research Institute, Vancouver, British Columbia V6T 1Z3, Canada.
Wang
Yanni
Y
Wong
Nelson K Y
NK
Le
Hoa T
HT
Pallen
Catherine J
CJ
Johnson
Pauline
P
D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D016399:Lymphoma, T-Cell / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000502:physiology*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry*
D011956:Receptors, Cell Surface; D014443:Tyrosine; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4