PMID- 31913659
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20231213
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 62
IP  - 5
DP  - 2020 May
TI  - Ste20-like Kinase-mediated Control of Actin Polymerization Is a New Mechanism for 
      Thin Filament-associated Regulation of Airway Smooth Muscle Contraction.
PG  - 645-656
LID - 10.1165/rcmb.2019-0310OC [doi]
AB  - It has been reported that actin polymerization is regulated by protein tyrosine 
      phosphorylation in smooth muscle on contractile stimulation. The role of protein 
      serine/threonine phosphorylation in modulating actin dynamics is 
      underinvestigated. SLK (Ste20-like kinase) is a serine/threonine protein kinase 
      that plays a role in apoptosis, cell cycle, proliferation, and migration. The 
      function of SLK in smooth muscle is mostly unknown. Here, SLK knockdown (KD) 
      inhibited acetylcholine (ACh)-induced actin polymerization and contraction 
      without affecting myosin light chain phosphorylation at Ser-19 in human airway 
      smooth muscle. Stimulation with ACh induced paxillin phosphorylation at Ser-272, 
      which was reduced in SLK KD cells. However, SLK did not catalyze paxillin Ser-272 
      phosphorylation in vitro. But, SLK KD attenuated Plk1 (polo-like kinase 1) 
      phosphorylation at Thr-210. Plk1 mediated paxillin phosphorylation at Ser-272 in 
      vitro. Expression of the nonphosphorylatable paxillin mutant S272A (substitution 
      of alanine at Ser-272) attenuated the agonist-enhanced F-actin/G-actin ratios 
      without affecting myosin light chain phosphorylation. Because N-WASP (neuronal 
      Wiskott-Aldrich Syndrome Protein) phosphorylation at Tyr-256 (an indication of 
      its activation) promotes actin polymerization, we also assessed the role of 
      paxillin phosphorylation in N-WASP activation. S272A paxillin inhibited the 
      ACh-enhanced N-WASP phosphorylation at Tyr-256. Together, these results suggest 
      that SLK regulates paxillin phosphorylation at Ser-272 via Plk1, which modulates 
      N-WASP activation and actin polymerization in smooth muscle. SLK-mediated actin 
      cytoskeletal reorganization may facilitate force transmission between the 
      contractile units and the extracellular matrix.
FAU - Wang, Yinna
AU  - Wang Y
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York.
FAU - Wang, Ruping
AU  - Wang R
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York.
FAU - Tang, Dale D
AU  - Tang DD
AUID- ORCID: 0000-0002-7339-9249
AD  - Department of Molecular and Cellular Physiology, Albany Medical College, Albany, 
      New York.
LA  - eng
GR  - R01 HL110951/HL/NHLBI NIH HHS/United States
GR  - R01 HL130304/HL/NHLBI NIH HHS/United States
GR  - R01 HL145392/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Actins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Myosin Light Chains)
RN  - 0 (Paxillin)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (WASL protein, human)
RN  - 0 (Wiskott-Aldrich Syndrome Protein, Neuronal)
RN  - 17885-08-4 (Phosphoserine)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 333DO1RDJY (Serotonin)
RN  - 820484N8I3 (Histamine)
RN  - EC 2.7.1.- (SLK protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
CIN - Am J Respir Cell Mol Biol. 2020 May;62(5):550-551. PMID: 31940442
MH  - Acetylcholine/pharmacology
MH  - Actin Cytoskeleton/drug effects/*metabolism
MH  - Actins/*metabolism
MH  - Adult
MH  - Biocatalysis/drug effects
MH  - Cell Cycle Proteins/metabolism
MH  - Female
MH  - Histamine/pharmacology
MH  - Humans
MH  - Lung/*physiology
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Multiprotein Complexes/metabolism
MH  - Muscle Contraction/drug effects/*physiology
MH  - Muscle, Smooth/drug effects/*physiology
MH  - Myosin Light Chains/metabolism
MH  - Paxillin/metabolism
MH  - Phosphorylation/drug effects
MH  - Phosphoserine/metabolism
MH  - Phosphotyrosine/metabolism
MH  - *Polymerization
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Serotonin/pharmacology
MH  - Wiskott-Aldrich Syndrome Protein, Neuronal/metabolism
MH  - Polo-Like Kinase 1
PMC - PMC7193783
OTO - NOTNLM
OT  - actin cytoskeleton
OT  - contraction
OT  - phosphorylation
OT  - signal transduction
OT  - smooth muscle
EDAT- 2020/01/09 06:00
MHDA- 2020/07/22 06:00
PMCR- 2021/05/01
CRDT- 2020/01/09 06:00
PHST- 2020/01/09 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2020/01/09 06:00 [entrez]
PHST- 2021/05/01 00:00 [pmc-release]
AID - 10.1165/rcmb.2019-0310OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2020 May;62(5):645-656. doi: 10.1165/rcmb.2019-0310OC.