ArticleBlood2016
p21-activated kinase 2 regulates HSPC cytoskeleton, migration, and homing via CDC42 activation and interaction with β-Pix.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Evaluation of translational potential of mRNA vaccine candidate antigens for pancreatic cancer: a systematic review based on clinical evidence and stratified prioritization strategies.Frontiers in immunology · 2026Pooled it
- Constructing advanced electrospun nanofiber/hydrogel composite scaffolds loading with nano hydroxyapatite and puerarin for promoting osseointegration and osteanagenesis in a rat cranial defect model.Materials today. Bio · 2026Article
- Endothelial β-PIX (ARHGEF7) supports actomyosin mediated expulsion of VWF through dynamic reorganization of the cytoskeleton.Molecular biology of the cell · 2026Article
- TOE1 is a β-catenin interacting protein regulating the proliferation of hematopoietic cells through PAK2 modulation.Stem cell reports · 2026Article
- PAK2 promotes CTC cluster formation by phosphorylating E-cadherin to enhance cell-cell adhesion in breast cancer.Breast cancer research : BCR · 2025Article
- PAK2-driven cytoskeleton-endosome dynamics control macrophage hyperphagia and SIRPA engagement.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Jund orchestratesProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- Molecular mechanisms of pancreatic cancer liver metastasis: the role of PAK2.Frontiers in immunology · 2024Article
- Targeting P21-activated kinase suppresses proliferation and enhances chemosensitivity in T-cell lymphoblastic lymphoma.Blood science (Baltimore, Md.) · 2023Article
- Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Circular RNA 0001789 sponges miR-140-3p and regulates PAK2 to promote the progression of gastric cancer.Journal of translational medicine · 2023Article
- Loss-of-Function of p21-Activated Kinase 2 Links BMP Signaling to Neural Tube Patterning Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- p21-Activated kinases as promising therapeutic targets in hematological malignancies.Leukemia · 2022Review
- Gene Biomarkers Related to Th17 Cells in Macular Edema of Diabetic Retinopathy: Cutting-Edge Comprehensive Bioinformatics Analysis andFrontiers in immunology · 2022Article
- Pak2 reduction induces a failure of early embryonic development in mice.Reproductive biology and endocrinology : RB&E · 2021Article
- A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness.Nature immunology · 2021Article
- Article
- hsa_circ_0013401 Accelerates the Growth and Metastasis and Prevents Apoptosis and Autophagy of Neuroblastoma Cells by Sponging miR-195 to Release PAK2.Oxidative medicine and cellular longevity · 2021Article
- NED416, a novel synthetic Sirt1 activator, promotes cutaneous wound healing via the MAPK/Rho pathway.International journal of molecular medicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cytoskeletal remodeling of hematopoietic stem and progenitor cells (HSPCs) is essential for homing to the bone marrow (BM). The Ras-related C3 botulinum toxin substrate (Rac)/cell division control protein 42 homolog (CDC42) effector p21-activated kinase (Pak2) has been implicated in HSPC homing and engraftment. However, the molecular pathways mediating Pak2 functions in HSPCs are unknown. Here, we demonstrate that both Pak2 kinase activity and its interaction with the PAK-interacting exchange factor-β (β-Pix) are required to reconstitute defective ITALIC! Pak2 (ITALIC! Δ/Δ)HSPC homing to the BM. Pak2 serine/threonine kinase activity is required for stromal-derived factor-1 (SDF1α) chemokine-induced HSPC directional migration, whereas Pak2 interaction with β-Pix is required to regulate the velocity of HSPC migration and precise F-actin assembly. Lack of SDF1α-induced filopodia and associated abnormal cell protrusions seen in ITALIC! Pak2 (ITALIC! Δ/Δ)HSPCs were rescued by wild-type (WT) Pak2 but not by a Pak2-kinase dead mutant (KD). Expression of a β-Pix interaction-defective mutant of Pak2 rescued filopodia formation but led to abnormal F-actin bundles. Although CDC42 has previously been considered an upstream regulator of Pak2, we found a paradoxical decrease in baseline activation of CDC42 in ITALIC! Pak2 (ITALIC! Δ/Δ)HSPCs, which was rescued by expression of Pak2-WT but not by Pak2-KD; defective homing of ITALIC! Pak2-deleted HSPCs was rescued by constitutive active CDC42. These data demonstrate that both Pak2 kinase activity and its interaction with β-Pix are essential for HSPC filopodia formation, cytoskeletal integrity, and homing via activation of CDC42. Taken together, we provide mechanistic insights into the role of Pak2 in HSPC migration and homing.
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Registered trials
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