title: Regulatory Crosstalk by Protein Kinases on CFTR Trafficking and Activity.
abstract: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e., channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease.
authors.affiliation: Faculty of Sciences, Biosystems and Integrative Sciences Institute, University of Lisboa Lisbon, Portugal.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Farinha
authors.affiliation: Department of Cell Biology, University of Pittsburgh School of MedicinePittsburgh, PA, USA; Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of MedicinePittsburgh, PA, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Swiatecka-Urban
authors.affiliation: Center for Cell Signaling and Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine Charlottesville, VA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Brautigan
authors.affiliation: Faculty of Sciences, Biosystems and Integrative Sciences Institute, University of LisboaLisbon, Portugal; Department of Human Genetics, National Health Institute Dr Ricardo JorgeLisbon, Portugal.
authors.forename: Peter
authors.initials: P
authors.lastname: Jordan
keywords: CFTR; cystic fibrosis; kinase; phosphorylation; protein trafficking
references.citation: J Biol Chem. 2011 Apr 1;286(13):11456-68
references.pmid: 21296876
references.citation: Cell Physiol Biochem. 2009;24(5-6):347-60
references.pmid: 19910675
references.citation: J Cell Biol. 2009 Mar 23;184(6):847-62
references.pmid: 19307599
references.citation: Amino Acids. 2013 Dec;45(6):1423-9
references.pmid: 24178769
references.citation: Biochem J. 2002 Sep 15;366(Pt 3):797-806
references.pmid: 12069690
references.citation: J Biol Chem. 2004 May 28;279(22):23542-9
references.pmid: 15044437
references.citation: J Biol Chem. 1993 Jan 25;268(3):2037-47
references.pmid: 7678414
references.citation: Genes Cells. 2008 May;13(5):483-95
references.pmid: 18429820
references.citation: Cell. 1991 Sep 6;66(5):1027-36
references.pmid: 1716180
references.citation: Mol Cell Biol. 2005 Jun;25(12):5242-52
references.pmid: 15923638
references.citation: Biochem Biophys Res Commun. 2007 Feb 16;353(3):535-40
references.pmid: 17194447
references.citation: Front Pharmacol. 2012 Sep 26;3:160
references.pmid: 23055971
references.citation: Genome Biol. 2003;4(5):111
references.pmid: 12734000
references.citation: Br Med Bull. 1992 Oct;48(4):754-65
references.pmid: 1281034
references.citation: Am J Physiol Lung Cell Mol Physiol. 2013 Oct 15;305(8):L530-41
references.pmid: 23934925
references.citation: Science. 2002 Dec 6;298(5600):1912-34
references.pmid: 12471243
references.citation: J Cell Biol. 2000 Aug 7;150(3):475-88
references.pmid: 10931861
references.citation: Autophagy. 2014;10 (11):2053-74
references.pmid: 25350163
references.citation: J Biol Chem. 1997 Feb 21;272(8):4978-84
references.pmid: 9030559
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D348-52
references.pmid: 23197659
references.citation: Biochem J. 2013 Jan 1;449(1):295-305
references.pmid: 23067305
references.citation: Pediatr Pulmonol. 2005 Jun;39(6):479-91
references.pmid: 15765539
references.citation: J Biol Chem. 2004 Sep 3;279(36):38025-31
references.pmid: 15247260
references.citation: FASEB J. 2015 Sep;29(9):3945-53
references.pmid: 26062600
references.citation: Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1764-9
references.pmid: 9620903
references.citation: Curr Pharm Des. 2013;19(19):3497-508
references.pmid: 23331027
references.citation: Nat Rev Immunol. 2010 Jun;10 (6):387-402
references.pmid: 20467426
references.citation: Nucleic Acids Res. 2003 Jan 1;31(1):383-7
references.pmid: 12520028
references.citation: Nature. 1993 Mar 11;362(6416):160-4
references.pmid: 7680769
references.citation: Curr Opin Nephrol Hypertens. 2004 Sep;13(5):557-62
references.pmid: 15300163
references.citation: Proteomics. 2015 Jan;15(2-3):447-61
references.pmid: 25330774
references.citation: Cell. 1991 Nov 15;67(4):775-84
references.pmid: 1718606
references.citation: Biochim Biophys Acta. 2012 Mar;1818(3):851-60
references.pmid: 22234285
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):663-8
references.pmid: 12522152
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4020-4
references.pmid: 17360470
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L497-507
references.pmid: 15557085
references.citation: Physiology (Bethesda). 2006 Oct;21:326-35
references.pmid: 16990453
references.citation: Annu Rev Physiol. 2008;70:329-55
references.pmid: 17961084
references.citation: J Biol Chem. 2010 Feb 26;285(9):6604-11
references.pmid: 20061383
references.citation: Genes Cells. 2004 Mar;9(3):219-32
references.pmid: 15005709
references.citation: PLoS One. 2013 Sep 18;8(9):e74232
references.pmid: 24058532
references.citation: Biochemistry. 2008 Jul 29;47(30):7925-36
references.pmid: 18597485
references.citation: FEBS Lett. 1997 Oct 13;416(1):27-9
references.pmid: 9369226
references.citation: Am J Physiol Renal Physiol. 2011 Aug;301(2):F410-9
references.pmid: 21613417
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1615-20
references.pmid: 16428287
references.citation: J Biol Chem. 2009 Feb 27;284(9):5645-53
references.pmid: 19095655
references.citation: Channels (Austin). 2016;10 (3):247-51
references.pmid: 26645934
references.citation: J Biol Chem. 2002 Dec 20;277(51):49605-12
references.pmid: 12393858
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18843-8
references.pmid: 21976485
references.citation: Mol Cell Biol. 2011 Oct;31(19):4076-86
references.pmid: 21807898
references.citation: Exp Cell Res. 2000 Jun 15;257(2):255-64
references.pmid: 10837139
references.citation: J Biol Chem. 2005 Nov 4;280(44):36762-72
references.pmid: 16131493
references.citation: Annu Rev Biochem. 2008;77:701-26
references.pmid: 18304008
references.citation: Eur J Immunol. 2012 Oct;42(10 ):2744-53
references.pmid: 22706924
references.citation: Nature. 1994 Sep 29;371(6496):423-6
references.pmid: 8090222
references.citation: EMBO J. 2006 Oct 4;25(19):4423-35
references.pmid: 16977309
references.citation: Am J Physiol Renal Physiol. 2013 Jul 1;305(1):F31-41
references.pmid: 23594824
references.citation: J Am Soc Nephrol. 2006 Jul;17 (7):1867-74
references.pmid: 16775035
references.citation: PLoS One. 2013;8(1):e54382
references.pmid: 23349870
references.citation: J Clin Invest. 2000 Jun;105(12):1711-21
references.pmid: 10862786
references.citation: Thorax. 2012 Jan;67(1):12-8
references.pmid: 21825083
references.citation: Methods Mol Biol. 2011;741:471-88
references.pmid: 21594802
references.citation: Nat Genet. 2013 Oct;45(10):1160-7
references.pmid: 23974870
references.citation: J Cyst Fibros. 2014 Jan;13(1):29-36
references.pmid: 23891399
references.citation: Am J Physiol Cell Physiol. 2001 Jan;280(1):C166-74
references.pmid: 11121388
references.citation: Annu Rev Cell Biol. 1992;8:67-113
references.pmid: 1282354
references.citation: J Biol Chem. 2009 Jul 3;284(27):18471-80
references.pmid: 19401467
references.citation: Am J Physiol Renal Physiol. 2005 Feb;288(2):F245-52
references.pmid: 15637347
references.citation: Biochem J. 2010 Jan 27;426(1):19-29
references.pmid: 19925455
references.citation: Nature. 1994 Sep 29;371(6496):419-23
references.pmid: 8090221
references.citation: BMC Cancer. 2010 Jun 22;10:315
references.pmid: 20569440
references.citation: Mol Cell Biol. 2011 Nov;31(22):4392-404
references.pmid: 21930781
references.citation: J Leukoc Biol. 1999 Nov;66(5):712-7
references.pmid: 10577498
references.citation: Commun Integr Biol. 2013 Mar 1;6(2):e23094
references.pmid: 23750297
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):390-5
references.pmid: 14695900
references.citation: Nat Genet. 2003 Dec;35(4):372-6
references.pmid: 14608358
references.citation: J Neurochem. 2012 May;121(3):327-8
references.pmid: 22224437
references.citation: Science. 2001 Aug 10;293(5532):1107-12
references.pmid: 11498583
references.citation: EMBO J. 1999 Mar 15;18(6):1492-505
references.pmid: 10075921
references.citation: J Cell Sci. 2007 Dec 15;120(Pt 24):4278-88
references.pmid: 18029400
references.citation: Kidney Int. 2006 Jun;69(12):2162-70
references.pmid: 16688122
references.citation: Am J Physiol Renal Physiol. 2015 Apr 1;308(7):F720-7
references.pmid: 25651566
references.citation: J Clin Invest. 2007 Apr;117(4):1078-87
references.pmid: 17380208
references.citation: J Biol Chem. 2014 May 23;289(21):15080-93
references.pmid: 24727471
references.citation: J Biol Chem. 2001 May 25;276(21):18066-74
references.pmid: 11278484
references.citation: Am J Physiol Cell Physiol. 2013 Jan 15;304(2):C164-9
references.pmid: 23114966
references.citation: Nat Neurosci. 2001 Apr;4(4):374-81
references.pmid: 11276227
references.citation: Oncogene. 2012 May 31;31(22):2773-82
references.pmid: 21996745
references.citation: Genome Res. 2012 Nov;22(11):2109-19
references.pmid: 22975805
references.citation: J Cell Biol. 2004 Mar 15;164(6):923-33
references.pmid: 15007060
references.citation: Cell Signal. 2013 Dec;25(12):2469-77
references.pmid: 23993962
references.citation: ACS Chem Biol. 2013 Feb 15;8(2):432-42
references.pmid: 23148778
references.citation: Oncogene. 2001 Sep 6;20(39):5562-9
references.pmid: 11571656
references.citation: FASEB J. 2003 Mar;17(3):349-68
references.pmid: 12631575
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2011 Oct;384(4-5):473-88
references.pmid: 21607646
references.citation: J Cell Sci. 2013 Jun 15;126(Pt 12):2692-703
references.pmid: 23572510
references.citation: Respiration. 2000;67(2):117-33
references.pmid: 10773783
references.citation: Mol Cell Proteomics. 2006 Nov;5(11):2124-30
references.pmid: 16887929
references.citation: Nature. 2005 Jul 7;436(7047):78-86
references.pmid: 15889048
references.citation: Am J Physiol. 1997 Jul;273(1 Pt 1):L127-33
references.pmid: 9252549
references.citation: Eur J Clin Invest. 2005 Jun;35(6):410-5
references.pmid: 15948903
references.citation: J Cyst Fibros. 2007 Jan;6(1):1-14
references.pmid: 17098482
references.citation: Cell. 1990 Nov 16;63(4):827-34
references.pmid: 1699669