title: Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.
abstract: T cell activation drives the protective immune response against pathogens, but is also critical for the development of pathological diseases in humans. Cytoskeletal changes are required for downstream functions in T cells, including proliferation, cytokine production, migration, spreading, and adhesion. Therefore, investigating the molecular mechanism of cytoskeletal changes is crucial for understanding the induction of T cell-driven immune responses and for developing therapies to treat immune disorders related to aberrant T cell activation. In this study, we used a plate-bound adhesion assay that incorporated near-infrared imaging technology to address how TCR signaling drives human T cell adhesion. Interestingly, we observed that T cells have weak adhesion early after TCR activation and that binding to the plate was significantly enhanced 30-60 minutes after receptor activation. This late stage of adhesion was mediated by actin polymerization but was surprisingly not dependent upon Src family kinase activity. By contrast, the non-catalytic functions of the kinases Fyn and Pyk2 were required for late stage human T cell adhesion. These data reveal a novel TCR-induced signaling pathway that controls cellular adhesion independent of the canonical TCR signaling cascade driven by tyrosine kinase activity.
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Chapman
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Yoder
authors.forename: Jon C D
authors.initials: JC
authors.lastname: Houtman
mesh_terms: D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D048430:Cell Shape / Q000502:physiology; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D000199:Actins; C494957:FYN protein, human; D051418:Focal Adhesion Kinase 2; D051076:Proto-Oncogene Proteins c-fyn