ArticleBlood2008
Pak1 regulates multiple c-Kit mediated Ras-MAPK gain-in-function phenotypes in Nf1+/- mast cells.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
51 citing papers in PubMed, 79 citations in OpenAlex.
- Regulation of Vascular Injury and Repair by P21-Activated Kinase 1 and P21-Activated Kinase 2: Therapeutic Potential and Challenges.Biomolecules · 2024Review
- TheCancers · 2024Review
- LC-MS/MS-based metabolomics and proteomics reveal the intervention of Kangnian decoction on the postoperative intestinal adhesion of rats.Frontiers in pharmacology · 2024Article
- PAK1 and Therapy Resistance in Melanoma.Cells · 2023Review
- RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.The Journal of investigative dermatology · 2023Review
- RAS and beyond: the many faces of the neurofibromatosis type 1 protein.Disease models & mechanisms · 2022Article
- Blockage of PAK1 alleviates the proliferation and invasion of NSCLC cells via inhibiting ERK and AKT signaling activity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Escherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in mice.Nature microbiology · 2021Article
- Deletion of P21-activated kinase-1 induces age-dependent increased visceral adiposity and cardiac dysfunction in female mice.Molecular and cellular biochemistry · 2021Article
- The Evolutionary Origins of Recurrent Pancreatic Cancer.Cancer discovery · 2020Article
- Polarization and sprouting of endothelial cells by angiopoietin-1 require PAK2 and paxillin-dependent Cdc42 activation.Molecular biology of the cell · 2019Article
- Kit-independent mast cell adhesion mediated by Notch.International immunology · 2019Article
- SLAP Is a Negative Regulator of FcεRI Receptor-Mediated Signaling and Allergic Response.Frontiers in immunology · 2019Article
- Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors.Nature microbiology · 2018Article
- PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1.Human molecular genetics · 2018Article
- Increased extracellular matrix deposition during chondrogenic differentiation of dental pulp stem cells from individuals with neurofibromatosis type 1: an in vitro 2D and 3D study.Orphanet journal of rare diseases · 2018Article
- A Collaborative Model for Accelerating the Discovery and Translation of Cancer Therapies.Cancer research · 2017Review
- The role of the immune system in neurofibromatosis type 1-associated nervous system tumors.CNS oncology · 2017Review
- The role of stem cells in benign tumors.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Contextual signaling in cancer.Seminars in cell & developmental biology · 2016Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations in the NF1 locus, which encodes neurofibromin, a negative regulator of Ras. Patients with NF1 develop numerous neurofibromas, which contain many inflammatory mast cells that contribute to tumor formation. Subsequent to c-Kit stimulation, signaling from Ras to Rac1/2 to the MAPK pathway appears to be responsible for multiple hyperactive mast cell phenotypes; however, the specific effectors that mediate these functions remain uncertain. p21-activated kinase 1 (Pak1) is a downstream mediator of Rac1/2 that has been implicated as a positive regulator of MAPK pathway members and is a modulator of cell growth and cytoskeletal dynamics. Using an intercross of Pak 1(-/-) mice with Nf1(+/-) mice, we determined that Pak1 regulates hyperactive Ras-dependent proliferation via a Pak1/Erk pathway, whereas a Pak1/p38 pathway is required for the increased migration in Nf1(+/-) mast cells. Furthermore, we confirmed that loss of Pak1 corrects the dermal accumulation of Nf1(+/-) mast cells in vivo to levels found in wild-type mice. Thus, Pak1 is a novel mast cell mediator that functions as a key node in the MAPK signaling network and potential therapeutic target in NF1 patients.
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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.