ArticleJournal of cell science2017
ARHGAP42 is activated by Src-mediated tyrosine phosphorylation to promote cell motility.
Article in Journal of cell science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Role of RhoGEFs or RhoGAPs in Pyk2-Mediated RhoA Activation in Depolarization-Induced Contraction of Rat Caudal Arterial Smooth Muscle.International journal of molecular sciences · 2025Article
- Sex differences in synaptic plasticity underlying learning.Journal of neuroscience research · 2023Review
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration.The Journal of cell biology · 2021Article
- A homozygous stop-gain variant in ARHGAP42 is associated with childhood interstitial lung disease, systemic hypertension, and immunological findings.PLoS genetics · 2021Article
- Spatial proximity of proteins surrounding zyxin under force-bearing conditions.Molecular biology of the cell · 2021Article
- The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia.Journal of translational medicine · 2021Article
- A Screen for PKN3 Substrates Reveals an Activating Phosphorylation of ARHGAP18.International journal of molecular sciences · 2020Article
- SASH1 suppresses triple-negative breast cancer cell invasion through YAP-ARHGAP42-actin axis.Oncogene · 2020Article
- Molecular Regulation of the RhoGAP GRAF3 and Its Capacity to Limit Blood Pressure In Vivo.Cells · 2020Article
- Overexpression of transcription factor Foxa1 and target genes remediate therapeutic protein production bottlenecks in Chinese hamster ovary cells.Biotechnology and bioengineering · 2020Article
- Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.Pharmacology & therapeutics · 2019Review
- BAR domain proteins-a linkage between cellular membranes, signaling pathways, and the actin cytoskeleton.Biophysical reviews · 2018Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The tyrosine kinase Src acts as a key regulator of cell motility by phosphorylating multiple protein substrates that control cytoskeletal and adhesion dynamics. In an earlier phosphotyrosine proteomics study, we identified a novel Rho-GTPase activating protein, now known as ARHGAP42, as a likely biologically relevant Src substrate. ARHGAP42 is a member of a family of RhoGAPs distinguished by tandem BAR-PH domains lying N-terminal to the GAP domain. Like other family members, ARHGAP42 acts preferentially as a GAP for RhoA. We show that Src principally phosphorylates ARHGAP42 on tyrosine 376 (Tyr-376) in the short linker between the BAR-PH and GAP domains. The expression of ARHGAP42 variants in mammalian cells was used to elucidate its regulation. We found that the BAR domain is inhibitory toward the GAP activity of ARHGAP42, such that BAR domain deletion resulted in decreased active GTP-bound RhoA and increased cell motility. With the BAR domain intact, ARHGAP42 GAP activity could be activated by phosphorylation of Tyr-376 to promote motile cell behavior. Thus, phosphorylation of ARHGAP42 Tyr-376 is revealed as a novel regulatory event by which Src can affect actin dynamics through RhoA inhibition.
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