ArticleProceedings of the National Academy of Sciences of the United States of America2002
Autoinhibition of the ligand-binding site of GGA1/3 VHS domains by an internal acidic cluster-dileucine motif.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 80 citations in OpenAlex.
- GGAs: Regulation of Multiple Sorting Pathways and Potential Association With Human Diseases.Journal of cellular and molecular medicine · 2026Review
- TOM1 family proteins: from cargo sorting to immune dysregulation and cancer.Cell communication and signaling : CCS · 2026Review
- Comprehensive characterization of V(D)J recombination from long-read transcriptomic data with VDJcraft.bioRxiv : the preprint server for biology · 2026Article
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- Emerging concepts of receptor endocytosis and concurrent intracellular signaling: Mechanisms of guanylyl cyclase/natriuretic peptide receptor-A activation and trafficking.Cellular signalling · 2019Review
- GGA2 interacts with EGFR cytoplasmic domain to stabilize the receptor expression and promote cell growth.Scientific reports · 2018Article
- Bidirectional apical-basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Trichosanthin increases Granzyme B penetration into tumor cells by upregulation of CI-MPR on the cell surface.Oncotarget · 2017Article
- An Analog-sensitive Version of the Protein Kinase Slt2 Allows Identification of Novel Targets of the Yeast Cell Wall Integrity Pathway.The Journal of biological chemistry · 2016Article
- Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs.Membranes · 2015Review
- Article
- Impact of genetic background on neonatal lethality of Gga2 gene-trap mice.G3 (Bethesda, Md.) · 2014Article
- A divalent interaction between HPS1 and HPS4 is required for the formation of the biogenesis of lysosome-related organelle complex-3 (BLOC-3).Biochimica et biophysica acta · 2013Article
- Role of adaptor proteins in secretory granule biogenesis and maturation.Frontiers in endocrinology · 2013Article
- Do GGA adaptors bind internal DXXLL motifs?Traffic (Copenhagen, Denmark) · 2012Article
- Analysis of Gga null mice demonstrates a non-redundant role for mammalian GGA2 during development.PloS one · 2012Article
- Structure of Golgi transport proteins.Cold Spring Harbor perspectives in biology · 2011Review
- Small peptide recognition sequence for intracellular sorting.Current opinion in biotechnology · 2010Review
- Functional characterization of protein-sorting machineries at the trans-Golgi network in Drosophila melanogaster.Journal of cell science · 2010Article
- Consortin, a trans-Golgi network cargo receptor for the plasma membrane targeting and recycling of connexins.Human molecular genetics · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-binding proteins) are a family of proteins implicated in protein trafficking from the Golgi to endosomes/lysosomes. These proteins have modular structures with an N-terminal VHS (VPS-27, Hrs, and STAM) domain followed by a GAT (GGA and TOM1) domain, a connecting hinge segment, and a C-terminal GAE (gamma-adaptin ear) domain. Isolated VHS domains have been shown to bind specifically to acidic cluster (AC)-dileucine motifs present in the cytoplasmic tails of the mannose 6-phosphate receptors. Here we report that full-length cytoplasmic GGA1 and GGA3 but not GGA2 bind the cation-independent mannose 6-phosphate receptor very poorly because of autoinhibition. This inhibition is caused by the binding of an AC-LL sequence present in the hinge segment to the ligand-binding site in the VHS domain. The inhibition depends on the phosphorylation of a serine located three residues upstream of the AC-LL motif. The serine is phosphorylated by casein kinase 2 in in vitro assays. Substitution of the GGA1 inhibitory sequence into the analogous location in GGA2, which lacks the AC-LL motif, results in autoinhibition of the latter protein. These data indicate that the activity of GGA1 and GGA3 is regulated by cycles of phosphorylation/dephosphorylation.
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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.