Regulation of taurine homeostasis by protein kinase CK₂ in mouse fibroblasts

TY - JOUR

T1 - Regulation of taurine homeostasis by protein kinase CK2 in mouse fibroblasts

AU - Hansen, Daniel Bloch

AU - Guerra, Barbara

AU - Jacobsen, Jack Hummeland

AU - Lambert, Ian Henry

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

KW - Animals

KW - Apoptosis

KW - Biological Transport

KW - Carcinoma, Ehrlich Tumor

KW - Casein Kinase II

KW - Cell Size

KW - Fibroblasts

KW - Gene Expression

KW - Homeostasis

KW - Kinetics

KW - Mice

KW - NADPH Oxidase

KW - NIH 3T3 Cells

KW - PTEN Phosphohydrolase

KW - Phosphatidylinositol 3-Kinases

KW - Phospholipases A2

KW - Protein Kinase Inhibitors

KW - Protein Tyrosine Phosphatases

KW - Reactive Oxygen Species

KW - Signal Transduction

KW - Taurine

KW - Tumor Cells, Cultured

KW - Water-Electrolyte Balance

U2 - 10.1007/s00726-010-0732-y

DO - 10.1007/s00726-010-0732-y

M3 - Journal article

C2 - 20827495

SN - 0939-4451

VL - 40

SP - 1091

EP - 1106

JO - Amino Acids

JF - Amino Acids

IS - 4

ER -