A supramolecular basis for CD45 tyrosine phosphatase regulation in sustained T cell activation.
Transmembrane protein tyrosine phosphatases, such as CD45, can act as both positive and negative regulators of cellular signaling. CD45 positively modulates T cell receptor (TCR) signaling by constitutively priming p56lck through the dephosphorylation of the C-terminal negative regulatory phosphotyrosine site. However, CD45 can also exert negative effects on cellular processes, including events triggered by integrin-mediated adhesion. To better understand these opposing actions of tyrosine phosphatases, the subcellular compartmentalization of CD45 was imaged by using laser scanning confocal microscopy during functional TCR signaling of live T lymphocytes. On antigen engagement, CD45 was first excluded from the central region of the interface between the T cell and the antigen-presenting surface where CD45 would inhibit integrin activation. Subsequently, CD45 was recruited back to the center of the contact to an area adjacent to the site of sustained TCR engagement. Thus, CD45 is well positioned within a supramolecular assembly in the vicinity of the engaged TCR, where CD45 would be able to maintain src-kinase activity for the duration of TCR engagement.
Johnson
K G
KG
Howard Hughes Medical Institute and Department of Pathology and Immunology, Washington University School of Medicine, St Louis MO 63110, USA.
Bromley
S K
SK
Dustin
M L
ML
Thomas
M L
ML
D000818:Animals; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens