ArticleMolecular and cellular biology2002
The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 150 citations in OpenAlex.
- PKCμ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication.iScience · 2024Article
- Expression of RAS and RAB interactor 1 (RIN1) in head and neck tumors at selected hospital in Ghana.PloS one · 2024Article
- Structural insights into regulation of the PEAK3 pseudokinase scaffold by 14-3-3.Nature communications · 2023Article
- Premalignant Oligodendrocyte Precursor Cells Stall in a Heterogeneous State of Replication Stress Prior to Gliomagenesis.Cancer research · 2021Article
- The Ins and Outs of RAS Effector Complexes.Biomolecules · 2021Review
- Role of RIN1 on telomerase activity driven by EGF-Ras mediated signaling in breast cancer.Experimental cell research · 2020Article
- Protein kinase D up-regulates transcription ofThe Journal of biological chemistry · 2019Article
- Effects of adult temperature on gene expression in a butterfly: identifying pathways associated with thermal acclimation.BMC evolutionary biology · 2019Article
- Protein kinase D2: a versatile player in cancer biology.Oncogene · 2018Review
- Lysophosphatidic acid via LPA-receptor 5/protein kinase D-dependent pathways induces a motile and pro-inflammatory microglial phenotype.Journal of neuroinflammation · 2017Article
- RIN1 promotes renal cell carcinoma malignancy by activating EGFR signaling through Rab25.Cancer science · 2017Article
- Protein kinase D1 (PKD1) phosphorylation on SerThe Journal of biological chemistry · 2017Article
- Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover.Molecular biology of the cell · 2017Article
- Activation of Mitofusin2 by Smad2-RIN1 Complex during Mitochondrial Fusion.Molecular cell · 2016Article
- An Inducible Retroviral Expression System for Tandem Affinity Purification Mass-Spectrometry-Based Proteomics Identifies Mixed Lineage Kinase Domain-like Protein (MLKL) as an Heat Shock Protein 90 (HSP90) Client.Molecular & cellular proteomics : MCP · 2016Article
- Tyrosine phosphorylation of RAS by ABL allosterically enhances effector binding.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Quantitative phosphoproteomics of cytotoxic T cells to reveal protein kinase d 2 regulated networks.Molecular & cellular proteomics : MCP · 2014Article
- The RAB5-GEF function of RIN1 regulates multiple steps during Listeria monocytogenes infection.Traffic (Copenhagen, Denmark) · 2014Article
- Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Protein kinase D interacts with neuronal nitric oxide synthase and phosphorylates the activatory residue serine 1412.PloS one · 2014Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Activation of RAS proteins can lead to multiple outcomes by virtue of regulated signal traffic through alternate effector pathways. We demonstrate that the RAS effector protein RIN1 binds to activated RAS with an affinity (K(d), 22 nM) similar to that observed for RAF1. At concentrations close to their equilibrium dissociation constant values, RIN1 and RAF1 compete directly for RAS binding. RIN1 was also observed to inhibit cellular transformation by activated mutant RAS. This distinguishes RIN1 from other RAS effectors, which are transformation enhancing. Blockade of transformation was mediated by the RAS binding domain but required membrane localization. RIN1 recognizes endogenous RAS following transient activation by epidermal growth factor, and a portion of RIN1 fractionates to the cell membrane in a manner consistent with a reversible interaction. RIN1 also binds to 14-3-3 proteins through a sequence including serine 351. Mutation of this residue abolished the 14-3-3 binding capacity of RIN1 and led to more efficient blockade of RAS-mediated transformation. The mutant protein, RIN1(S351A), showed a shift in localization to the plasma membrane. Serine 351 is a substrate for protein kinase D (PKD [also known as PKCmu]) in vitro and in vivo. These data suggest that the normal localization and function of RIN1, as well as its ability to compete with RAF, are regulated in part by 14-3-3 binding, which in turn is controlled by PKD phosphorylation.
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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.