Cofilin: a missing link between T cell co-stimulation and rearrangement of the actin cytoskeleton.
The actin cytoskeletal network plays a regulatory role in receptor-mediated signal-transducing events. Recently, we have shown that the small actin-depolymerizing protein cofilin represents a component of a co-stimulatory signaling pathway in human T cells. Cofilin is dephosphorylated on phosphoserine residues following co-stimulation via accessory receptors such as CD2, CD4, CD8 or CD28, but not in response to TCR engagement alone. Here we demonstrate that accessory receptor triggering induces the transient association of cofilin with the actin cytoskeleton. Only the dephosphorylated form of cofilin binds to cytoskeletal actin in vivo. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 block dephosphorylation of cofilin and its association with the actin cytoskeleton. These results suggest that cofilin provides an as yet missing link between functionally crucial T cell surface receptors and rearrangements of the actin cytoskeleton.
Lee
K H
KH
Institute for Immunology, Ruprecht-Karls-University, Heidelberg, Germany.
Meuer
S C
SC
Samstag
Y
Y
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008840:Microfilament Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D000077191:Wortmannin
D051339:Actin Depolymerizing Factors; D000199:Actins; D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000077191:Wortmannin