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Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity

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Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity. / Luz, Simao; Kongsuphol, Patthara; Mendes, Ana Isabel; Romeiras, Francisco; Sousa, Marisa; Schreiber, Rainer; Matos, Paulo; Jordan, Peter; Mehta, Anil; Amaral, Margarida D.; Kunzelmann, Karl; Farinha, Carlos M.

In: Molecular and Cellular Biology, Vol. 31, No. 22, 11.2011, p. 4392-4404.

Research output: Contribution to journalArticle

Harvard

Luz, S, Kongsuphol, P, Mendes, AI, Romeiras, F, Sousa, M, Schreiber, R, Matos, P, Jordan, P, Mehta, A, Amaral, MD, Kunzelmann, K & Farinha, CM 2011, 'Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity' Molecular and Cellular Biology, vol 31, no. 22, pp. 4392-4404.

APA

Luz, S., Kongsuphol, P., Mendes, A. I., Romeiras, F., Sousa, M., Schreiber, R., Matos, P., Jordan, P., Mehta, A., Amaral, M. D., Kunzelmann, K., & Farinha, C. M. (2011). Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity. Molecular and Cellular Biology, 31(22), 4392-4404doi: 10.1128/MCB.05517-11

Vancouver

Luz S, Kongsuphol P, Mendes AI, Romeiras F, Sousa M, Schreiber R et al. Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity. Molecular and Cellular Biology. 2011 Nov;31(22):4392-4404.

Author

Luz, Simao; Kongsuphol, Patthara; Mendes, Ana Isabel; Romeiras, Francisco; Sousa, Marisa; Schreiber, Rainer; Matos, Paulo; Jordan, Peter; Mehta, Anil; Amaral, Margarida D.; Kunzelmann, Karl; Farinha, Carlos M. / Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity.

In: Molecular and Cellular Biology, Vol. 31, No. 22, 11.2011, p. 4392-4404.

Research output: Contribution to journalArticle

Bibtex - Download

@article{8017bfe7cf964e02b1e45b629bfcb501,
title = "Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity",
author = "Simao Luz and Patthara Kongsuphol and Mendes, {Ana Isabel} and Francisco Romeiras and Marisa Sousa and Rainer Schreiber and Paulo Matos and Peter Jordan and Anil Mehta and Amaral, {Margarida D.} and Karl Kunzelmann and Farinha, {Carlos M.}",
year = "2011",
volume = "31",
number = "22",
pages = "4392--4404",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity

A1 - Luz,Simao

A1 - Kongsuphol,Patthara

A1 - Mendes,Ana Isabel

A1 - Romeiras,Francisco

A1 - Sousa,Marisa

A1 - Schreiber,Rainer

A1 - Matos,Paulo

A1 - Jordan,Peter

A1 - Mehta,Anil

A1 - Amaral,Margarida D.

A1 - Kunzelmann,Karl

A1 - Farinha,Carlos M.

AU - Luz,Simao

AU - Kongsuphol,Patthara

AU - Mendes,Ana Isabel

AU - Romeiras,Francisco

AU - Sousa,Marisa

AU - Schreiber,Rainer

AU - Matos,Paulo

AU - Jordan,Peter

AU - Mehta,Anil

AU - Amaral,Margarida D.

AU - Kunzelmann,Karl

AU - Farinha,Carlos M.

PY - 2011/11

Y1 - 2011/11

N2 - Previously, the pleiotropic "master kinase" casein kinase 2 (CK2) was shown to interact with CFTR, the protein responsible for cystic fibrosis (CF). Moreover, CK2 inhibition abolished CFTR conductance in cell-attached membrane patches, native epithelial ducts, and Xenopus oocytes. CFTR possesses two CK2 phosphorylation sites (S422 and T1471), with unclear impact on its processing and trafficking. Here, we investigated the effects of mutating these CK2 sites on CFTR abundance, maturation, and degradation coupled to effects on ion channel activity and surface expression. We report that CK2 inhibition significantly decreased processing of wild-type (wt) CFTR, with no effect on F508del CFTR. Eliminating phosphorylation at S422 and T1471 revealed antagonistic roles in CFTR trafficking: S422 activation versus T1471 inhibition, as evidenced by a severe trafficking defect for the T1471D mutant. Notably, mutation of Y512, a consensus sequence for the spleen tyrosine kinase (SYK) possibly acting in a CK2 context adjacent to the common CF-causing defect F508del, had a strong effect on both maturation and CFTR currents, allowing the identification of this kinase as a novel regulator of CFTR. These results reinforce the importance of CK2 and the S422 and T1471 residues for regulation of CFTR and uncover a novel regulation of CFTR by SYK, a recognized controller of inflammation.

AB - Previously, the pleiotropic "master kinase" casein kinase 2 (CK2) was shown to interact with CFTR, the protein responsible for cystic fibrosis (CF). Moreover, CK2 inhibition abolished CFTR conductance in cell-attached membrane patches, native epithelial ducts, and Xenopus oocytes. CFTR possesses two CK2 phosphorylation sites (S422 and T1471), with unclear impact on its processing and trafficking. Here, we investigated the effects of mutating these CK2 sites on CFTR abundance, maturation, and degradation coupled to effects on ion channel activity and surface expression. We report that CK2 inhibition significantly decreased processing of wild-type (wt) CFTR, with no effect on F508del CFTR. Eliminating phosphorylation at S422 and T1471 revealed antagonistic roles in CFTR trafficking: S422 activation versus T1471 inhibition, as evidenced by a severe trafficking defect for the T1471D mutant. Notably, mutation of Y512, a consensus sequence for the spleen tyrosine kinase (SYK) possibly acting in a CK2 context adjacent to the common CF-causing defect F508del, had a strong effect on both maturation and CFTR currents, allowing the identification of this kinase as a novel regulator of CFTR. These results reinforce the importance of CK2 and the S422 and T1471 residues for regulation of CFTR and uncover a novel regulation of CFTR by SYK, a recognized controller of inflammation.

KW - Animals

KW - Intracellular Signaling Peptides and Proteins

KW - Ion Channels

KW - Protein-Tyrosine Kinases

KW - Mice

KW - Casein Kinase II

KW - Xenopus laevis

KW - Phosphorylation

KW - Cystic Fibrosis Transmembrane Conductance Regulator

KW - Mice, Inbred C57BL

KW - Cyclic AMP-Dependent Protein Kinases

KW - Mutation

KW - Cricetinae

KW - Protein Transport

U2 - 10.1128/MCB.05517-11

DO - 10.1128/MCB.05517-11

M1 - Article

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 22

VL - 31

SP - 4392

EP - 4404

ER -

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