Smooth Muscle Myosin Phosphatase-associated Kinase Induces Ca2+ Sensitization via Myosin Phosphatase Inhibition

Borman, Meredith A.; MacDonald, Justin A.; Murányi, Andrea; Hartshorne, David J.; Haystead, Timothy A.J.

doi:10.1074/jbc.m201597200

Cited by 87 publications

(108 citation statements)

References 32 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…When phosphorylated by PKC, CPI-17 becomes a potent inhibitor of type 1 protein Ser/Thr phosphatases, such as myosin phosphatase PP1. CPI-17 may also be phosphorylated by RhoK (31), by ILK (24), and by ZIP-like kinase (8).…”

Section: Intermediate Proteinsmentioning

confidence: 99%

“…3): a small 20-kDa subunit of uncertain function (M20), a 38-kDa catalytic subunit, which is a type 1 phosphatase (PP1), and a myosin-targeting subunit (MYPT1) of 110 -133 kDa (9,32). MYPT1 may be phosphorylated by ILK (8), by ZIP-like kinase (8), and in some muscles, MYPT1 may be phosphorylated by Rho kinase (RhoK), inhib-iting phosphatase activity and promoting contraction. RhoK, however, plays no role in ACh-induced contraction of Eso, because the contraction is not affected by either C3, an exoenzyme of Clostridium botulinum that is a specific RhoA inhibitor (14), or by the RhoK inhibitor Y27632 (W. Cao, unpublished observations).…”

Section: Intermediate Proteinsmentioning

confidence: 99%

See 1 more Smart Citation

Signal-Transduction Pathways that Regulate Smooth Muscle Function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles

Harnett

Cao

Biancani

2005

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Section: Intermediate Proteinsmentioning

confidence: 99%

Section: Intermediate Proteinsmentioning

confidence: 99%

Signal-Transduction Pathways that Regulate Smooth Muscle Function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles

Harnett

Cao

Biancani

2005

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

“…The major site of MYPT1 phosphorylation is Threonine 696 (numbering relates to the human form), which inhibits phosphatase function [57], possibly by blocking the active site or by disrupting interaction of the catalytic subunit with phosphorylated substrate [58]. Kinases that have been reported to phosphorylate Thr696 include: ROCK1 and ROCK2 [57], MRCKa and MRCKb [47,59], ILK [60,61], ZIPK [62] and the DMPK [63]. Phosphorylation of Threonine 853 by ROCK has also been reported to inhibit MLC dephosphorylation by decreasing MLC binding [57,64].…”

Section: Acto-myosin Contractionmentioning

confidence: 99%

The actin cytoskeleton in cancer cell motility

Olson

Sahai

2008

Clin Exp Metastasis

475

392

View full text Add to dashboard Cite

Cancer cell metastasis is a multi-stage process involving invasion into surrounding tissue, intravasation, transit in the blood or lymph, extravasation, and growth at a new site. Many of these steps require cell motility, which is driven by cycles of actin polymerization, cell adhesion and acto-myosin contraction. These processes have been studied in cancer cells in vitro for many years, often with seemingly contradictory results. The challenge now is to understand how the multitude of in vitro observations relates to the movement of cancer cells in living tumour tissue. In this review we will concentrate on actin protrusion and acto-myosin contraction. We will begin by presenting some general principles summarizing the widely-accepted mechanisms for the co-ordinated regulation of actin polymerization and contraction. We will then discuss more recent studies that investigate how experimental manipulation of actin dynamics affects cancer cell invasion in complex environments and in vivo.

show abstract

“…The Thr-697 site of MYPT1 (rat sequence) has been identified as a key inhibitory phosphorylation site for the regulation of MLCP activity. Rho-associated kinase (ROK) (25), zipper-interacting protein kinase (ZIPK) (3,24,34,40), and integrin-linked kinase (ILK) (28, 39) have been demonstrated to phosphorylate MYPT1 at this inhibitory site. In addition, ROK (32), ZIPK (35), and ILK (9) contribute indirectly to MLCP inhibition by playing a role in CPI-17 phosphorylation.…”

Section: ϩmentioning

confidence: 99%

Characterization of protein kinase pathways responsible for Ca²⁺sensitization in rat ileal longitudinal smooth muscle

Ihara¹,

Moffat²,

Ostrander³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

View full text Add to dashboard Cite

2ϩsensitization in rat ileal longitudinal smooth muscle. Am J Physiol Gastrointest Liver Physiol 293: G699-G710, 2007. First published July 26, 2007; doi:10.1152/ajpgi.00214.2007.-We investigated the protein kinases responsible for myosin regulatory light chain (LC20) phosphorylation and regulation of myosin light chain phosphatase (MLCP) activity during microcystin (phosphatase inhibitor)-induced contraction at low Ca 2ϩ concentrations of rat ileal smooth muscle stretched in the longitudinal axis. Application of 1 M microcystin induced LC20 diphosphorylation and contraction of ␤-escin-permeabilized rat ileal smooth muscle at pCa 9. The PKC inhibitor GF109203x, the MEK inhibitor PD-98059, and the p38 MAPK inhibitor SB-203580 significantly reduced this contraction. These inhibitory effects were abolished when the microcystin concentration was increased to 10 M, indicating that application of these kinase inhibitors generated an increase in MLCP activity. GF-109203x and PD-98059, but not SB-203580, significantly decreased the phosphorylation level of the myosin-targeting subunit of MLCP, MYPT1, at Thr-697 (rat sequence) during microcystin-induced contraction at pCa 9. On the other hand, SB-203580, but not GF-109203x or PD-98059, significantly reduced the phosphorylation level of the PKC-potentiated phosphatase inhibitor of 17 kDa (CPI-17). A zipper-interacting protein kinase (ZIPK) inhibitor (SM1 peptide) and a Rho-associated kinase inhibitor (Y-27632) had little effect on microcystin-induced contraction at pCa 9. In conclusion, PKC, ERK1/2, and p38 MAPK pathways facilitate microcystin-induced contraction at low Ca 2ϩ concentrations by contributing to the inhibition of MLCP activity either through phosphorylation of MYPT1 or CPI-17 [probably mediated by integrin-linked kinase (ILK)]. ILK and not ZIPK is likely to be the protein kinase responsible for LC20 diphosphorylation during microcystin-induced contraction of rat ileal smooth muscle at pCa 9, similar to its recently described role in vascular smooth muscle. The negative regulation of MLCP by PKC and MAPKs during microcystin-induced contraction at pCa 9, which is not observed in vascular smooth muscle, may be unique to phasic smooth muscle. ileum; protein kinase C; myosin phosphatase; mitogen-activated protein kinase; protein kinase C-potentiated phosphatase inhibitor protein of 17 kDa; myosin-targeting subunit of myosin light chain phosphatase SMOOTH MUSCLE CONTRACTION is a dynamic and highly regulated process. The contractile state of smooth muscle is mainly regulated by phosphorylation of the 20-kDa myosin regulatory light chain (LC 20 ] i )} is the primary determinant of smooth muscle contraction. Force can be further increased through signaling pathways that modulate MLCK and/or MLCP activities. The Ca 2ϩ sensitivity of contraction can be affected by any change in the ratio of MLCK:MLCP activity. A decrease in MLCP activity will shift the balance in favor of MLCK, resulting in a greater degree of LC 20 phosphorylation and contraction. The phenomenon of ...

show abstract

Smooth Muscle Myosin Phosphatase-associated Kinase Induces Ca2+ Sensitization via Myosin Phosphatase Inhibition

Cited by 87 publications

References 32 publications

Signal-Transduction Pathways that Regulate Smooth Muscle Function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles

Signal-Transduction Pathways that Regulate Smooth Muscle Function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles

The actin cytoskeleton in cancer cell motility

Characterization of protein kinase pathways responsible for Ca²⁺sensitization in rat ileal longitudinal smooth muscle

Contact Info

Product

Resources

About

Smooth Muscle Myosin Phosphatase-associated Kinase Induces Ca2+ Sensitization via Myosin Phosphatase Inhibition

Cited by 87 publications

References 32 publications

Signal-Transduction Pathways that Regulate Smooth Muscle Function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles

Signal-Transduction Pathways that Regulate Smooth Muscle Function I. Signal transduction in phasic (esophageal) and tonic (gastroesophageal sphincter) smooth muscles

The actin cytoskeleton in cancer cell motility

Characterization of protein kinase pathways responsible for Ca2+sensitization in rat ileal longitudinal smooth muscle

Contact Info

Product

Resources

About

Characterization of protein kinase pathways responsible for Ca²⁺sensitization in rat ileal longitudinal smooth muscle