Abstract:
: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).
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Ambach A,Saunus J,Konstandin M,Wesselborg S,Meuer SC,Samstag Ydoi
10.1002/1521-4141(2000012)30:12<3422::AID-IMMU3422keywords:
subject
Has Abstractpub_date
2000-12-01 00:00:00pages
3422-31issue
12eissn
0014-2980issn
1521-4141pii
10.1002/1521-4141(2000012)30:12<3422::AID-IMMU3422journal_volume
30pub_type
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journal_title:European journal of immunology
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更新日期:1998-04-01 00:00:00
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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