Beta1 integrin-mediated T cell adhesion and cell spreading are regulated by calpain.
To investigate the function of calpain in T cells, we sought to determine the role of this protease in cellular events mediated by beta1 integrins. T cell receptor cross-linked or phorbol ester-stimulated T cells binding to immobilized fibronectin induce the translocation of calpain to the cytoskeletal/membrane fraction of these cells. Such translocation of calpain is associated with proteolytic modification of protein tyrosine phosphatase 1B, increased cellular adhesion, and dramatic alterations in cellular morphology. However, affinity-related increases in T cell adhesion induced by the anti-beta1 integrin antibody 8A2 occur in a calpain-independent manner and in the absence of morphological shape changes. Furthermore, calpain undergoes activation in response to either alpha4beta1 or alpha5beta1 integrin binding to fibronectin in appropriately stimulated T cells, and calpain II as well as protein tyrosine phosphatase 1B accumulates at sites of focal contact formation. Inhibition of calpain activity not only inhibits the proteolytic modification of protein tyrosine phosphatase 1B, but also decreases the ability of T cells to adhere to and spread on immobilized fibronectin. Thus, we describe a potential regulatory role for calpain in beta1 integrin-mediated signaling events associated with T cell adhesion and cell spreading on fibronectin.
Rock
M T
MT
Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Dix
A R
AR
Brooks
W H
WH
Roszman
T L
TL
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000502:physiology; D002154:Calpain / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D005353:Fibronectins; D019012:Integrin beta1; C071482:calpeptin; D002154:Calpain; D013755:Tetradecanoylphorbol Acetate