The serine phosphatases PP1 and PP2A associate with and activate the actin-binding protein cofilin in human T lymphocytes

✍ Scribed by Andreas Ambach; Jochen Saunus; Mathias Konstandin; Sebastian Wesselborg; Stefan C. Meuer; Yvonne Samstag

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 192 KB
• Volume: 30
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(2000012)30:12<3422::aid-immu3422>3.0.co;2-j

✦ Synopsis

Cofilin, an actin-depolymerizing protein, is essential for the functional dynamics of the actin cytoskeleton and for cell viability. In unstimulated human peripheral blood T lymphocytes cofilin is phosphorylated and localized in the cytoplasm. Following co-stimulation through accessory receptors (e.g. CD2 or CD28) -however, not following TCR/CD3 stimulation alone -cofilin undergoes dephosphorylation. The subcellular localization as well as the actinbinding activity of cofilin are regulated by the phosphorylation state of serine-3. Thus, only the dephosphorylated form of cofilin associates with the actin cytoskeleton and possesses the capability to translocate into the nucleus. Recently, LIM-kinase 1 was shown to inactivate cofilin through phosphorylation. Here, we have identified the functional counterparts of LIM-kinase 1: the serine/threonine phosphatases of type 1 and type 2A not only associate with cofilin but also dephosphorylate this 19-kDa protein and thereby mediate cofilin activation. In malignant T lymphoma cells, activation of these phosphatases occurs spontaneously, independent of external stimuli. In untransformed human peripheral blood T lymphocytes, these phosphatases function through a cyclosporin A/FK506-resistant co-stimulatory signaling pathway which is common for the accessory receptors CD2 and CD28. This costimulatory signaling pathway is also not affected by a series of other clinically established immunosuppressive drugs (i.e. rapamycin, dexamethasone, leflunomide or mycophenolic acid).