Inhibition of constitutive serine phosphatase activity in T lymphoma cells results in phosphorylation of pp19/cofilin and induces apoptosis.
In untransformed T lymphocytes, pp19/cofilin, a cytoplasmic actin-binding protein, undergoes dephosphorylation and nuclear translocation in response to costimulation through accessory receptors (e.g., CD2), but not following TCR/CD3 triggering. In malignant T lymphoma cells, dephosphorylation and nuclear translocation of pp19/cofilin occur spontaneously through constitutive activation of a serine phosphatase. Blockade of these processes by the serine phosphatase inhibitor okadaic acid leads to apoptosis. Moreover, lowering the intracellular pp19/cofilin concentrations by antisense-cofilin transfection results in reduced cloning efficiencies. These findings provide support for the view that pp19/cofilin plays a critical role in the growth and survival of both untransformed and malignant T lymphocytes.
Samstag
Y
Y
Institute for Immunology, Ruprecht-Karls-University, Heidelberg, Germany.
Dreizler
E M
EM
Ambach
A
A
Sczakiel
G
G
Meuer
S C
SC
D051339:Actin Depolymerizing Factors; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D016373:DNA, Antisense / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008840:Microfilament Proteins; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D051339:Actin Depolymerizing Factors; D016373:DNA, Antisense; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases