Quantitative profiling of spreading-coupled protein tyrosine phosphorylation in migratory cells

Xie, Yajun; Wang, Jinlong; Zhang, Yuanya; Liu, Xiaofei; Wang, Xiaorong; Liu, Kehui; Huang, Xiahe; Wang, Yingchun

doi:10.1038/srep31811

Cited by 6 publications

(6 citation statements)

References 33 publications

(56 reference statements)

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“…Tyrosine phosphorylation can regulate adhesion complexes by inducing conformational changes or facilitating the binding of additional proteins including regulatory enzymes, for example, through phosphotyrosine binding domains. Increased tyrosine phosphorylation can correlate with both cell–cell [ 31–34 ] and cell–matrix [ 35 ] adhesion formation and disassembly. Adhesion remodelling can be initiated by a number of stimuli such as mechanical force [ 36 ], reactive oxygen species (ROS) [ 37 ] or growth factors and cytokines [ 38 , 39 ].…”

Section: Ptps and Cell Adhesion Complexesmentioning

confidence: 99%

Protein tyrosine phosphatases in cell adhesion

Young

Biggins

Sharpe

2021

Biochemical Journal

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Adhesive structures between cells and with the surrounding matrix are essential for the development of multicellular organisms. In addition to providing mechanical integrity, they are key signalling centres providing feedback on the extracellular environment to the cell interior, and vice versa. During development, mitosis and repair, cell adhesions must undergo extensive remodelling. Post-translational modifications of proteins within these complexes serve as switches for activity. Tyrosine phosphorylation is an important modification in cell adhesion that is dynamically regulated by the protein tyrosine phosphatases (PTPs) and protein tyrosine kinases. Several PTPs are implicated in the assembly and maintenance of cell adhesions, however, their signalling functions remain poorly defined. The PTPs can act by directly dephosphorylating adhesive complex components or function as scaffolds. In this review, we will focus on human PTPs and discuss their individual roles in major adhesion complexes, as well as Hippo signalling. We have collated PTP interactome and cell adhesome datasets, which reveal extensive connections between PTPs and cell adhesions that are relatively unexplored. Finally, we reflect on the dysregulation of PTPs and cell adhesions in disease.

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Section: Ptps and Cell Adhesion Complexesmentioning

confidence: 99%

Protein tyrosine phosphatases in cell adhesion

Young

Biggins

Sharpe

2021

Biochemical Journal

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“…Phosphorylations in tyrosine residues control cell signaling and regulate a variety of biological processes, including the reorganization of the cytoskeleton [79,80]. We previously reported an uncharacterized tyrosine phosphorylation event in NMHC2A triggered by bacterial infections [30].…”

Section: Discussionmentioning

confidence: 99%

Src-Dependent NM2A Tyrosine Phosphorylation Regulates Actomyosin Remodeling

Brito

Pereira

Mesquita

et al. 2023

Cells

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Non-muscle myosin 2A (NM2A) is a key cytoskeletal enzyme that, along with actin, assembles into actomyosin filaments inside cells. NM2A is fundamental for cell adhesion and motility, playing important functions in different stages of development and during the progression of viral and bacterial infections. Phosphorylation events regulate the activity and the cellular localization of NM2A. We previously identified the tyrosine phosphorylation of residue 158 (pTyr158) in the motor domain of the NM2A heavy chain. This phosphorylation can be promoted by Listeria monocytogenes infection of epithelial cells and is dependent on Src kinase; however, its molecular role is unknown. Here, we show that the status of pTyr158 defines cytoskeletal organization, affects the assembly/disassembly of focal adhesions, and interferes with cell migration. Cells overexpressing a non-phosphorylatable NM2A variant or expressing reduced levels of Src kinase display increased stress fibers and larger focal adhesions, suggesting an altered contraction status consistent with the increased NM2A activity that we also observed. We propose NM2A pTyr158 as a novel layer of regulation of actomyosin cytoskeleton organization.

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“…pTyr events are essential to respond to extracellular stimuli and regulate key cellular processes, including the reorganization of cytoskeleton [38,39]. We previously reported an uncharacterized pTyr event on NMHC2A, triggered by different bacterial infections [20].…”

Section: Discussionmentioning

confidence: 99%

“…pTyr controls cell signaling and regulates a variety of biological processes, including the reorganization of the cytoskeleton [44, 45]. We previously reported an uncharacterized pTyr event on NMHC2A, triggered by bacterial infections [25].…”

Section: Discussionmentioning

confidence: 99%

Src-dependent NM2A tyrosine-phosphorylation regulates actomyosin dynamics

Brito

Mesquita

Osório

et al. 2020

Preprint

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Non-muscle myosin 2A (NM2A) is a key cytoskeletal enzyme that along with actin assembles into actomyosin filaments inside cells. NM2A is fundamental in cellular processes requiring force generation such as cell adhesion, motility and cell division, and plays important functions in different stages of development and during the progression of viral and bacterial infections. We previously identified at the motor domain of the NM2A, a novel Src-dependent tyrosine phosphorylation on residue 158 (pTyr158), which is promoted by Listeria monocytogenes infection. Despite the central role of NM2A in several cell biology processes, the pTyr at this specific residue had never been reported. Here we showed that LLO, a toxin secreted by Listeria, is sufficient to trigger NM2A pTyr158 by activating Src, which coordinates actomyosin remodeling. We further addressed the role of NM2A pTyr158 on the organization and dynamics of the actomyosin cytoskeleton and found that by controlling the activation of the NM2A, the status of the pTyr158 alters cytoskeletal organization, dynamics of focal adhesions and cell motility, without affecting NM2A enzymatic activity in vitro. Ultimately, by using Caenorhabditis elegans as a model to assess the role of this pTyr158 in vivo, we found that the status of the pTyr158 has implications in gonad function and is required for organism survival under stress conditions. We conclude that the fine control of the NM2A pTyr158 is required for cell cytoskeletal remodeling and dynamics, and we propose Src-dependent NM2A pTyr158 as a novel layer of regulation of the actomyosin cytoskeleton.

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Quantitative profiling of spreading-coupled protein tyrosine phosphorylation in migratory cells

Cited by 6 publications

References 33 publications

Protein tyrosine phosphatases in cell adhesion

Protein tyrosine phosphatases in cell adhesion

Src-Dependent NM2A Tyrosine Phosphorylation Regulates Actomyosin Remodeling

Src-dependent NM2A tyrosine-phosphorylation regulates actomyosin dynamics

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