ArticlePloS one2012
The PDZ protein GIPC regulates trafficking of the LPA1 receptor from APPL signaling endosomes and attenuates the cell's response to LPA.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 37 citations in OpenAlex.
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- Myosin VI drives arrestin-independent internalization and signaling of GPCRs.Nature communications · 2024Article
- LPAR1 regulates enteric nervous system function through glial signaling and contributes to chronic intestinal pseudo-obstruction.The Journal of clinical investigation · 2022Article
- Molecular Regulation of Lysophosphatidic Acid Receptor 1 Maturation and Desensitization.Cell biochemistry and biophysics · 2021Review
- The LPAInternational journal of molecular sciences · 2021Review
- Compartmentalized GPCR Signaling from Intracellular Membranes.The Journal of membrane biology · 2021Review
- Strength and duration of GIPC-dependent signaling networks as determinants in cancer.Neoplasia (New York, N.Y.) · 2021Review
- Tyrosine-Based Signals Regulate the Assembly of Daple⋅PARD3 Complex at Cell-Cell Junctions.iScience · 2020Article
- Autophagy-Mediated Exosomes as Immunomodulators of Natural Killer Cells in Pancreatic Cancer Microenvironment.Frontiers in oncology · 2020Review
- Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer.Cancers · 2019Review
- Article
- Endocytosis is required for CThe Journal of biological chemistry · 2018Article
- The MYO6 interactome reveals adaptor complexes coordinating early endosome and cytoskeletal dynamics.EMBO reports · 2018Article
- α5β1 integrin trafficking and Rac activation are regulated by APPL1 in a Rab5-dependent manner to inhibit cell migration.Journal of cell science · 2018Article
- APPL1 is a multifunctional endosomal signaling adaptor protein.Biochemical Society transactions · 2017Review
- MYO6 Regulates Spatial Organization of Signaling Endosomes Driving AKT Activation and Actin Dynamics.Cell reports · 2017Article
- The neuropilin 2 isoform NRP2b uniquely supports TGFβ-mediated progression in lung cancer.Science signaling · 2017Article
- Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Lysophosphatidic acid (LPA) mediates diverse cellular responses through the activation of at least six LPA receptors--LPA(1-6,) but the interacting proteins and signaling pathways that mediate the specificity of these receptors are largely unknown. We noticed that LPA(1) contains a PDZ binding motif (SVV) identical to that present in two other proteins that interact with the PDZ protein GIPC. GIPC is involved in endocytic trafficking of several receptors including TrkA, VEGFR2, lutropin and dopamine D2 receptors. Here we show that GIPC binds directly to the PDZ binding motif of LPA(1) but not that of other LPA receptors. LPA(1) colocalizes and coimmunoprecipitates with GIPC and its binding partner APPL, an activator of Akt signaling found on APPL signaling endosomes. GIPC depletion by siRNA disturbed trafficking of LPA(1) to EEA1 early endosomes and promoted LPA(1) mediated Akt signaling, cell proliferation, and cell motility. We propose that GIPC binds LPA(1) and promotes its trafficking from APPL-containing signaling endosomes to EEA1 early endosomes and thus attenuates LPA-mediated Akt signaling from APPL endosomes.
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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.