Regulation of integrin-mediated T cell adhesion by the transmembrane protein tyrosine phosphatase CD45.
The transmembrane protein tyrosine phosphatase CD45 is required for Ag receptor signal transduction in lymphocytes. Recently, a role for CD45 in the regulation of macrophage adhesion has been demonstrated as well. To investigate further the role of CD45 in the regulation of adhesion, we examined integrin-mediated adhesion to fibronectin of two T cell lines and their CD45-deficient variants. The absence of CD45 correlated with enhanced adhesion to fibronectin via integrin alpha5beta1 (VLA-5), but not alpha4beta1 (VLA-4) in both cell lines. Adhesion returned to normal levels upon transfection of wild-type CD45 into the CD45-deficient lines. Transfection of chimeric or mutant molecules expressing some, but not all, CD45 domains and activities demonstrated that both the transmembrane domain and the tyrosine phosphatase activity of CD45 were required for regulation of integrin-dependent adhesion, but the highly glycosylated extracellular domain was dispensable. In contrast, only a catalytically active CD45 cytoplasmic domain was required for TCR signaling. Transfectants that restored normal levels of adhesion to fibronectin coimmunoprecipitated with the transmembrane protein known as CD45-associated protein. These studies demonstrate a novel role for CD45 in adhesion regulation and suggest a possible function for its association with CD45-associated protein.
Shenoi
H
H
Division of Infectious Diseases, Department of Molecular Microbiology, Howard Hughes Medical Institute, St. Louis, MO 63110, USA.
Seavitt
J
J
Zheleznyak
A
A
Thomas
M L
ML
Brown
E J
EJ
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D005110:Extracellular Space / Q000201:enzymology / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000502:physiology*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C090519:PTPRCAP protein, human; D010446:Peptide Fragments; D010750:Phosphoproteins; C513303:Ptprcap protein, mouse; D017469:Receptors, Fibronectin; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases