ArticleScientific reports2018
Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Squamoid Eccrine Ductal Carcinoma Displays Ultraviolet Mutations and Intermediate Gene Expression Relative to Squamous Cell Carcinoma, Microcystic Adnexal Carcinoma, and Porocarcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Article
- Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex.Journal of chemical theory and computation · 2023Article
- Identifying and overcoming the sampling challenges in relative binding free energy calculations of a model protein:protein complex.bioRxiv : the preprint server for biology · 2023Article
- Rab22a Promotes Epithelial-Mesenchymal Transition in Papillary Thyroid Carcinoma by Activating PI3K/AKT/mTOR Signaling Pathway.BioMed research international · 2022Article
- The orchestrated signaling by PI3Kα and PTEN at the membrane interface.Computational and structural biotechnology journal · 2022Review
- Cancer-associated mutations in the p85α N-terminal SH2 domain activate a spectrum of receptor tyrosine kinases.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Conformationally active integrin endocytosis and traffic: why, where, when and how?Biochemical Society transactions · 2020Review
- Impact of p85α Alterations in Cancer.Biomolecules · 2019Review
- Insight into the PTEN - p85α interaction and lipid binding properties of the p85α BH domain.Oncotarget · 2018Article
- Isoform-specific activities of the regulatory subunits of phosphatidylinositol 3-kinases - potentially novel therapeutic targets.Expert opinion on therapeutic targets · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity. Three other p85α mutations (E137K, K288Q, E297K) also altered the regulation of PTEN catalytic activity. In contrast, many p85α mutations reduced the binding to Rab5 (L30F, I69L, I82F, I177N, E217K), and several impacted the GAP activity of p85α towards Rab5 (E137K, I177N, E217K, E297K). We determined the crystal structure of several of these p85α BH domain mutants (E137K, E217K, R262T E297K) for bovine p85α BH and found that the mutations did not alter the overall domain structure. Thus, several p85α mutations found in human cancers may deregulate PTEN and/or Rab5 regulated pathways to contribute to oncogenesis. We also engineered several experimental mutations within the p85α BH domain and identified L191 and V263 as important for both binding and regulation of Rab5 activity.
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