ArticleScience signaling2011
SH3 domain-based phototrapping in living cells reveals Rho family GAP signaling complexes.
Article in Science signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
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- The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development.Scientific reports · 2019Article
- Gephyrin: a key regulatory protein of inhibitory synapses and beyond.Histochemistry and cell biology · 2018Review
- Emerging Mechanisms Underlying Dynamics of GABAergic Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Review
- Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins: A SYSTEMATIC APPROACH TOWARD SELECTIVE INACTIVATION OF RHO FAMILY PROTEINS.The Journal of biological chemistry · 2016Article
- SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses.Neuron · 2016Article
- Hypertension: the missing WNKs.American journal of physiology. Renal physiology · 2016Review
- Endocytic membrane turnover at the leading edge is driven by a transient interaction between Cdc42 and GRAF1.Journal of cell science · 2015Article
- The genesis of tyrosine phosphorylation.Cold Spring Harbor perspectives in biology · 2014Review
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- Plexin structures are coming: opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions.Cellular and molecular life sciences : CMLS · 2012Review
- Modified SH2 domain to phototrap and identify phosphotyrosine proteins from subcellular sites within cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- The application of modular protein domains in proteomics.FEBS letters · 2012Review
- Gephyrin, the enigmatic organizer at GABAergic synapses.Frontiers in cellular neuroscience · 2012Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Rho family GAPs [guanosine triphosphatase (GTPase) activating proteins] negatively regulate Rho family GTPase activity and therefore modulate signaling events that control cytoskeletal dynamics. The spatial distribution of these GAPs and their specificity toward individual GTPases are controlled by their interactions with various proteins within signaling complexes. These interactions are likely mediated through the Src homology 3 (SH3) domain, which is abundant in the Rho family GAP proteome and exhibits a micromolar binding affinity, enabling the Rho family GAPs to participate in transient interactions with multiple binding partners. To capture these elusive GAP signaling complexes in situ, we developed a domain-based proteomics approach, starting with in vivo phototrapping of SH3 domain-binding proteins and the mass spectrometry identification of associated proteins for nine representative Rho family GAPs. After the selection of candidate binding proteins by cluster analysis, we performed peptide array-based high-throughput in vitro binding assays to confirm the direct interactions and map the SH3 domain-binding sequences. We thereby identified 54 SH3-mediated binding interactions (including 51 previously unidentified ones) for nine Rho family GAPs. We constructed Rho family GAP interactomes that provided insight into the functions of these GAPs. We further characterized one of the predicted functions for the Rac-specific GAP WRP and identified a role for WRP in mediating clustering of the postsynaptic scaffolding protein gephyrin and the GABA(A) (γ-aminobutyric acid type A) receptor at inhibitory synapses.
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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.