ArticleThe Journal of cell biology2015
PAK4 promotes kinase-independent stabilization of RhoU to modulate cell adhesion.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- Rab12 is a regulator of mitophagy and mitochondrial homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- Neddylation-dependent RAB40-Cullin5 E3 ligase complex controls ubiquitin-mediated proteasomal degradation of DNAJC13.BBA advances · 2026Article
- Rab40 GTPases regulate AMBRA1-mediated transcription and cell migration.Journal of cell science · 2025Article
- Mechanisms and therapeutic potential of disulphidptosis in cancer.Cell proliferation · 2025Review
- Atypical RhoUV GTPases in development and disease.Biochemical Society transactions · 2024Review
- Molecular basis and current insights of atypical Rho small GTPase in cancer.Molecular biology reports · 2024Review
- RhoU forms homo-oligomers to regulate cellular responses.Journal of cell science · 2024Article
- Peripheral Neuropathy and Decreased Locomotion of aExperimental neurobiology · 2023Article
- A Rab-bit hole: Rab40 GTPases as new regulators of the actin cytoskeleton and cell migration.Frontiers in cell and developmental biology · 2023Review
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4).Communications biology · 2022Article
- LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability.Cellular & molecular biology letters · 2022Article
- Review
- Rab40c regulates focal adhesions and PP6 activity by controlling ANKRD28 ubiquitylation.Life science alliance · 2022Article
- PAK-dependent regulation of actin dynamics in breast cancer cells.The international journal of biochemistry & cell biology · 2022Review
- Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration.The Journal of cell biology · 2022Article
- Regulation of GTPase function by autophosphorylation.Molecular cell · 2022Article
- The significance of PAK4 in signaling and clinicopathology: A review.Open life sciences · 2022Review
- Role of RhoC in cancer cell migration.Cancer cell international · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
P21-activated kinase 4 (PAK4) is a Cdc42 effector protein thought to regulate cell adhesion disassembly in a kinase-dependent manner. We found that PAK4 expression is significantly higher in high-grade human breast cancer patient samples, whereas depletion of PAK4 modifies cell adhesion dynamics of breast cancer cells. Surprisingly, systematic analysis of PAK4 functionality revealed that PAK4-driven adhesion turnover is neither dependent on Cdc42 binding nor kinase activity. Rather, reduced expression of PAK4 leads to a concomitant loss of RhoU expression. We report that RhoU is targeted for ubiquitination by the Rab40A-Cullin 5 complex and demonstrate that PAK4 protects RhoU from ubiquitination in a kinase-independent manner. Overexpression of RhoU rescues the PAK4 depletion phenotype, whereas loss of RhoU expression reduces cell adhesion turnover and migration. These data support a new kinase-independent mechanism for PAK4 function, where an important role of PAK4 in cellular adhesions is to stabilize RhoU protein levels. Thus, PAK4 and RhoU cooperate to drive adhesion turnover and promote cell migration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.