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

Eur J Immunol. 2000 Dec;30(12):3422-31. doi: 10.1002/1521-4141(2000012)30:12<3422::AID-IMMU3422>3.0.CO;2-J.


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 actin-binding 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 co-stimulatory signaling pathway is also not affected by a series of other clinically established immunosuppressive drugs (i.e. rapamycin, dexamethasone, leflunomide or mycophenolic acid).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors
  • Cyclosporine / pharmacology
  • Dexamethasone / pharmacology
  • Humans
  • Isoxazoles / pharmacology
  • Leflunomide
  • Microfilament Proteins / metabolism*
  • Mycophenolic Acid / pharmacology
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / physiology*
  • Phosphorylation
  • Sirolimus / pharmacology
  • T-Lymphocytes / metabolism*
  • Tacrolimus / pharmacology


  • Actin Depolymerizing Factors
  • Isoxazoles
  • Microfilament Proteins
  • Okadaic Acid
  • Dexamethasone
  • Cyclosporine
  • Phosphoprotein Phosphatases
  • Leflunomide
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus