PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and cell chemotaxis

Even-Faitelson, Liron; Rosenberg, Michael K.; Ravid, Shoshana

doi:10.1016/j.cellsig.2004.12.015

Cited by 38 publications

(39 citation statements)

References 45 publications

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“…Nevertheless, we clearly demonstrate a distinct subcellular distribution of the recombinant myosin IIA proteins in line with previous reports. 26,43 Our findings and those of others indicate that future work is necessary to understand exactly how phosphorylation affects the organization and turnover of myosin II filaments in vivo.…”

Section: Discussionmentioning

confidence: 88%

TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

Clark

Middelbeek

Lasonder

et al. 2008

Journal of Molecular Biology

125

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Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian α-kinase TRPM7 inhibits myosin II-based contractility in a Ca 2+ -and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOHtermini of both mouse and human myosin IIA heavy chains-the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the α-helical tail of the myosin IIA heavy chain.

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Section: Discussionmentioning

confidence: 88%

TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

Clark

Middelbeek

Lasonder

et al. 2008

Journal of Molecular Biology

125

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“…The IP-PAK1 was used to phosphorylate 10 g MBP, NMHC II-A, or NMHC II-B in an in vitro activity assay described previously (Even-Faitelson et al, 2005). The samples were separated on SDS-PAGE, and the extent of phosphorylation was measured by counting the bands in a scintillation counter.…”

Section: Immunoprecipitation Of Pak1 From Tsu-pr1 Cells and In Vitro mentioning

confidence: 99%

“…Cells, 5 ϫ 10 5 , were starved to serum as described previously (Even-Faitelson et al, 2005) and then stimulated with 7 ng ml Ϫ1 EGF for 0, 1, or 4 min. At the indicated time points, the plated cells were washed with ice-cold phosphatebuffered saline (PBS) and then collected in 300 l sonication buffer (50 mM Tris-HCl, pH 7.5, 50 mM NaCl, 1 mM DTT, 2 mM EDTA, Protease Inhibitors Cocktail).…”

Section: Coimmunoprecipitation Gel Electrophoresis and Western Blotmentioning

confidence: 99%

“…Immunoprecipitation of PAK1 from TSU-pr1 cells was carried out as described previously (Even-Faitelson et al, 2005). The IP-PAK1 was used to phosphorylate 10 g MBP, NMHC II-A, or NMHC II-B in an in vitro activity assay described previously (Even-Faitelson et al, 2005).…”

Section: Immunoprecipitation Of Pak1 From Tsu-pr1 Cells and In Vitro mentioning

confidence: 99%

“…Recently, van Leeuwen et al (1999) have shown that PAK1 is involved in the bradykinin-dependent phosphorylation of NMHC in PC12 cells. Moreover, we have recently shown that PAK1 is involved in the regulation of myosin II-B phosphorylation, localization, and filament assembly (Even-Faitelson et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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PAK1 and aPKCζ Regulate Myosin II-B Phosphorylation: A Novel Signaling Pathway Regulating Filament Assembly

Even-Faitelson

Ravid

2006

MBoC

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Many signaling pathways regulate the function of the cellular cytoskeleton. Yet we know very little about the proteins involved in the cross-talk between the signaling and the cytoskeletal systems. Here we show that myosin II-B, an important cytoskeletal protein, resides in a complex with p21-activated kinase 1 (PAK1) and atypical protein kinase C (PKC) zeta (aPKC) and that the interaction between these proteins is EGF-dependent. We further show that PAK1 is involved in aPKC phosphorylation and that aPKC phosphorylates myosin II-B directly on a specific serine residue in an EGF-dependent manner. This latter phosphorylation is specific to isoform B of myosin II, and it leads to slower filament assembly of myosin II-B. Furthermore, a decrease in aPKC expression in the cells alters myosin II-B cellular organization. Our finding of a new signaling pathway involving PAK1, aPKC, and myosin II-B, which is implicated in myosin II-B filament assembly and cellular organization, provides an important link between the signaling system and cytoskeletal dynamics.

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Role of p21‐activated kinase in cell polarity and directional mesendoderm migration in the Xenopus gastrula

Nagel

Luu

Bisson

et al. 2009

Developmental Dynamics

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PAK1 regulates myosin II-B phosphorylation, filament assembly, localization and cell chemotaxis

Cited by 38 publications

References 45 publications

TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

PAK1 and aPKCζ Regulate Myosin II-B Phosphorylation: A Novel Signaling Pathway Regulating Filament Assembly

Role of p21‐activated kinase in cell polarity and directional mesendoderm migration in the Xenopus gastrula

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