Polo-like Kinase 1 Regulates Vimentin Phosphorylation at Ser-56 and Contraction in Smooth Muscle.
Polo-like kinase 1 (Plk1) is a serine/threonine-protein kinase that has been implicated in mitosis, cytokinesis, and smooth muscle cell proliferation. The role of Plk1 in smooth muscle contraction has not been investigated. Here, stimulation with acetylcholine induced Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activated Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor. Moreover, knockdown of Plk1 in smooth muscle attenuated force development. Smooth muscle conditional knock-out of Plk1 also diminished contraction of mouse tracheal rings. Plk1 knockdown inhibited acetylcholine-induced vimentin phosphorylation at Ser-56 without affecting myosin light chain phosphorylation. Expression of T210A Plk1 inhibited the agonist-induced vimentin phosphorylation at Ser-56 and contraction in smooth muscle. However, myosin light chain phosphorylation was not affected by T210A Plk1. Ste20-like kinase (SLK) is a serine/threonine-protein kinase that has been implicated in spindle orientation and microtubule organization during mitosis. In this study knockdown of SLK inhibited Plk1 phosphorylation at Thr-210 and activation. Finally, asthma is characterized by airway hyperresponsiveness, which largely stems from airway smooth muscle hyperreactivity. Here, smooth muscle conditional knock-out of Plk1 attenuated airway resistance and airway smooth muscle hyperreactivity in a murine model of asthma. Taken together, these findings suggest that Plk1 regulates smooth muscle contraction by modulating vimentin phosphorylation at Ser-56. Plk1 activation is regulated by SLK during contractile activation. Plk1 contributes to the pathogenesis of asthma.
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208.
Jia
J
Li
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208.
Ruping
R
Wang
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208.
Olivia J
OJ
Gannon
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208.
Alyssa C
AC
Rezey
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208.
Sixin
S
Jiang
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208.
Brennan D
BD
Gerlach
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208.
Guoning
G
Liao
From the Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York 12208 tangd@mail.amc.edu.
Dale D
http://orcid.org/0000-0002-7339-9249
DD
Tang
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014132:Trachea / Q000502:physiology; D014746:Vimentin / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014746:Vimentin; D000097869:Polo-Like Kinase 1
cytoskeleton; excitation-contraction coupling (E-C coupling); intermediate filament; phosphorylation; signal transduction; smooth muscle
Nat Rev Mol Cell Biol. 2009 Apr;10(4):265-75
19305416
Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L240-8
16997882
Nat Struct Mol Biol. 2013 Sep;20(9):1047-53
23893132
J Cell Biol. 2014 Jun 23;205(6):791-9
24958772
J Biol Chem. 2014 May 16;289(20):14157-69
24700464
Annu Rev Physiol. 1989;51:299-313
2653184
J Biol Chem. 2002 Nov 15;277(46):44115-20
12207013
Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a002543
20066089
J Cardiovasc Pharmacol Ther. 2008 Jun;13(2):130-40
18212360
Am J Physiol Cell Physiol. 2009 Aug;297(2):C299-309
19494238
Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a000125
20182611
J Cell Physiol. 2012 Feb;227(2):739-50
21465480
Acta Physiol Scand. 1998 Dec;164(4):341-8
9887957
Biochem J. 2005 Jun 15;388(Pt 3):773-83
15766329
Philos Trans R Soc Lond B Biol Sci. 2004 Dec 29;359(1452):1921-30
15647168
J Cardiovasc Pharmacol Ther. 2009 Jun;14(2):89-98
19329671
J Biol Chem. 2013 Jul 12;288(28):20713-22
23740246
Am J Respir Cell Mol Biol. 2014 Nov;51(5):652-9
24818551
Respir Res. 2016 Jul 25;17(1):91
27457922
J Biol Chem. 2006 Nov 10;281(45):34716-24
16990256
Am J Physiol Cell Physiol. 2009 Dec;297(6):C1424-33
19812368
Clin Cancer Res. 2009 May 1;15(9):3094-102
19383823
Curr Opin Pharmacol. 2004 Jun;4(3):230-4
15140413
Am J Physiol Cell Physiol. 2007 Sep;293(3):C993-1002
17596300
Mol Biol Cell. 2013 Oct;24(20):3205-14
23985322
Respir Res. 2013 Oct 11;14:105
24112389
Biochemistry. 2008 Mar 25;47(12):3688-96
18298087
Respir Res. 2015 Oct 30;16:134
26517982
J Biol Chem. 2015 Apr 3;290(14):8913-24
25713069
Am J Respir Cell Mol Biol. 2013 Feb;48(2):172-8
23087049
Mol Membr Biol. 2002 Apr-Jun;19(2):81-94
12126234
Circ Res. 2007 Aug 17;101(4):420-8
17615370
Am J Physiol Cell Physiol. 2010 Sep;299(3):C630-7
20610769
J Cell Physiol. 2014 Oct;229(10):1484-93
24648251
Am J Physiol Cell Physiol. 2006 Sep;291(3):C483-9
16571866
Respir Res. 2015 Aug 05;16:93
26242183
J Biol Chem. 2011 Feb 4;286(5):3630-44
21071443
Int J Cancer. 2011 Dec 1;129(11):2744-55
21538350
Eur J Cell Biol. 1995 Sep;68(1):62-9
8549591
Br J Pharmacol. 2003 Dec;140(7):1159-62
14597600
Dev Cell. 2008 May;14(5):646-59
18477449
Am J Physiol Cell Physiol. 2014 Apr 15;306(8):C753-61
24477238
Am J Physiol Cell Physiol. 2008 Apr;294(4):C869-78
18256275
J Biol Chem. 2015 May 1;290(18):11403-16
25759389
Am J Physiol Cell Physiol. 2008 Sep;295(3):C768-78
18596213
Nat Rev Mol Cell Biol. 2004 Jun;5(6):429-40
15173822
Am J Physiol Cell Physiol. 2008 Sep;295(3):C576-87
18596210