Regulation of taurine homeostasis by protein kinase CK2 in mouse fibroblasts.
Increased expression of the ubiquitous serine/threonine protein kinase CK2 has been associated with increased proliferative capacity and increased resistance towards apoptosis. Taurine is the primary organic osmolyte involved in cell volume control in mammalian cells, and shift in cell volume is a critical step in cell proliferation, differentiation and induction of apoptosis. In the present study, we use mouse NIH3T3 fibroblasts and Ehrlich Lettré ascites tumour cells with different CK2 expression levels. Taurine uptake via the Na(+) dependent transporter TauT and taurine release are increased and reduced, respectively, following pharmacological CK2 inhibition. The effect of CK2 inhibition on TauT involves modulation of transport kinetics, whereas the effect on the taurine release pathway involves reduction in the open-probability of the efflux pathway. Stimulation of PLA(2) activity, exposure to exogenous reactive oxygen species as well as inhibition of protein tyrosine phosphotases (PTP) potentiate the swelling-induced taurine loss. Inhibition of PI3K and PTEN reduces and potentiates swelling-induced taurine release, respectively. Inhibition of CK2 has no effect on PLA(2) activity and ROS production by NADPH oxidase, whereas it lifts the effect of PTEN and PTP inhibition. It is suggested that CK2 regulates the taurine release downstream to known swelling-induced signal transducers including PLA(2), NADPH oxidase and PI3K.
Hansen
Daniel Bloch
DB
Department of Biology, Section for Cell and Developmental Biology, University of Copenhagen, Copenhagen Ø, Denmark.
Guerra
Barbara
B
Jacobsen
Jack Hummeland
JH
Lambert
Ian Henry
IH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006706:Homeostasis; D007700:Kinetics; D051379:Mice; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013654:Taurine / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014882:Water-Electrolyte Balance / Q000187:drug effects
D047390:Casein Kinase II; D019255:NADPH Oxidases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054467:Phospholipases A2; D047428:Protein Kinase Inhibitors; D017027:Protein Tyrosine Phosphatases; D017382:Reactive Oxygen Species; D013654:Taurine; C487757:Pten protein, mouse