Phosphorylation of Serine 402 Regulates RacGAP Protein Activity of FilGAP Protein

Morishita, Yoshitaka; Tsutsumi, Koji; Ohta, Yasutaka

doi:10.1074/jbc.m115.666875

Cited by 19 publications

(31 citation statements)

References 37 publications

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“…As another example, phosphorylation of the RAC-specific GAP FilGAP (filamin A-associated RhoGAP; also known as ARHGAP24) on Ser402, which is C-terminal to the RhoGAP domain, switches its subcellular localization from the cytoskeletal network to the cytoplasm, where it undergoes activation and subsequently inactivates RAC1 (REF. 102). This results in the decreased spreading of HeLa cells on fibronectin, and cell adhesion to fibronectin induces dephosphorylation of FilGAP at Ser402 (REF.…”

Section: Regulation Of Gapsmentioning

confidence: 99%

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Regulating Rho GTPases and their regulators

Hodge

Ridley²

2016

Nat Rev Mol Cell Biol

731

657

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Rho GTPases regulate cytoskeletal and cell adhesion dynamics and thereby coordinate a wide range of cellular processes, including cell migration, cell polarity and cell cycle progression. Most Rho GTPases cycle between a GTP-bound active conformation and a GDP-bound inactive conformation to regulate their ability to activate effector proteins and to elicit cellular responses. However, it has become apparent that Rho GTPases are regulated by post-translational modifications and the formation of specific protein complexes, in addition to GTP-GDP cycling. The canonical regulators of Rho GTPases - guanine nucleotide exchange factors, GTPase-activating proteins and guanine nucleotide dissociation inhibitors - are regulated similarly, creating a complex network of interactions to determine the precise spatiotemporal activation of Rho GTPases.

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Section: Regulation Of Gapsmentioning

confidence: 99%

“…This results in the decreased spreading of HeLa cells on fibronectin, and cell adhesion to fibronectin induces dephosphorylation of FilGAP at Ser402 (REF. 102). …”

Section: Regulation Of Gapsmentioning

confidence: 99%

Regulating Rho GTPases and their regulators

Hodge

Ridley²

2016

Nat Rev Mol Cell Biol

731

657

View full text Add to dashboard Cite

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“…We have shown previously that FilGAP is phosphorylated downstream of Rho/ROCK‐signaling and involved in Rho‐mediated inactivation of Rac . FilGAP therefore plays a role in the mesenchymal to amoeboid transition of carcinoma cells .…”

Section: Discussionmentioning

confidence: 94%

“…FilGAP also binds Filamin A and Filamin A is localized at the lamella of moving cells . The PH domain of FilGAP also interacts with activated Arf6 and Arf6 is shown to be involved in the regulation of leukocyte chemotaxis . It will be interesting to determine how these signaling are involved in the regulation of FilGAP.…”

Section: Discussionmentioning

confidence: 99%

“…FilGAP is a Rac‐specific GAP that regulates cell polarity through Rac‐dependent suppression of lamellae formation . FilGAP is phosphorylated downstream of Rho/ROCK signaling, and this phosphorylation stimulates its RacGAP activity . Depletion of endogenous FilGAP in MDA‐MB‐231 breast carcinoma cells induced a Rac‐dependent elongated mesenchymal morphology.…”

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confidence: 99%

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The RacGAP protein FilGAP is a negative regulator of chemokine‐promoted lymphocyte migration

et al. 2016

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Rho family small GTPases regulate lymphocyte migration induced by chemokines. However, how lymphocyte migration is regulated by Rho GTPases remains to be elucidated. Here, we identified FilGAP, a Rac‐specific GAP, as a negative regulator of lymphocyte polarization and migration. Depletion of FilGAP in mouse pro‐B BAF cells increased cellular elongation and membrane protrusion after stimulation of the cells with SDF‐1α, which caused increased migration speed. Although FilGAP is detectable both at the front and rear of polarized cells, FilGAP appears to be concentrated at the tip of retracting lamellae of moving lymphocytes. Moreover, depletion of FilGAP increased activation of Rac at the front of polarized cells. Thus, FilGAP may inhibit lamellae extension at the front of moving lymphocytes.

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