ArticleProceedings of the National Academy of Sciences of the United States of America1998
Identification of the binding site for Gqalpha on its effector Bruton's tyrosine kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 56 citations in OpenAlex.
- IGF1 Binding to Integrin αvβ3 Induces Direct Gα13 Binding to IGF1R Kinase.International journal of molecular sciences · 2026Article
- Uveal melanoma following Bruton's tyrosine inhibitor use for the treatment of hematologic malignancies.American journal of ophthalmology case reports · 2025Article
- Pseudoangiosarcoma and cutaneous collagenous vasculopathy in a patient on a Bruton's tyrosine kinase inhibitor.JAAD case reports · 2024Article
- Structural basis and mechanism of activation of two different families of G proteins by the same GPCR.Nature structural & molecular biology · 2021Article
- Serotonin/HTR1E signaling blocks chronic stress-promoted progression of ovarian cancer.Theranostics · 2021Article
- The zinc-binding region of IL-2 inducible T cell kinase (Itk) is required for interaction with Gα13 and activation of serum response factor.The international journal of biochemistry & cell biology · 2013Article
- Article
- G alpha(q) acts as an adaptor protein in protein kinase C zeta (PKCzeta)-mediated ERK5 activation by G protein-coupled receptors (GPCR).The Journal of biological chemistry · 2010Article
- The Tec family kinase Itk exists as a folded monomer in vivo.The Journal of biological chemistry · 2009Article
- Interplay between the heterotrimeric G-protein subunits Galphaq and Galphai2 sets the threshold for chemotaxis and TCR activation.BMC immunology · 2009Article
- Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR.The EMBO journal · 2007Article
- Article
- Altered levels of Gq activity modulate axonal pathfinding in Drosophila.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002Article
- Competing modes of self-association in the regulatory domains of Bruton's tyrosine kinase: intramolecular contact versus asymmetric homodimerization.Protein science : a publication of the Protein Society · 2002Article
- Metabotropic glutamate receptor 5-induced phosphorylation of extracellular signal-regulated kinase in astrocytes depends on transactivation of the epidermal growth factor receptor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2001Article
- Neuropeptide-induced androgen independence in prostate cancer cells: roles of nonreceptor tyrosine kinases Etk/Bmx, Src, and focal adhesion kinase.Molecular and cellular biology · 2001Article
- Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk.BMC immunology · 2001Article
- Signaling network of the Btk family kinases.Oncogene · 2000Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterotrimeric G proteins and tyrosine kinases are two major cellular signal transducers. Although G proteins are known to activate tyrosine kinases, the activation mechanism is not clear. Here, we demonstrate that G protein Gqalpha binds directly to the nonreceptor Bruton's tyrosine kinase (Btk) to a region composed of a Tec-homology (TH) domain and a sarcoma virus tyrosine kinase (Src)-homology 3 (SH3) domain both in vitro and in vivo. Only active GTP-bound Gqalpha, not inactive GDP-bound Gqalpha, can bind to Btk. Mutations of Btk that disrupt its ability to bind Gqalpha also eliminate Btk stimulation by Gqalpha, suggesting that this interaction is important for Btk activation. Remarkably, the structure of this TH (including a proline-rich sequence) -SH3 fragment of the Btk family of tyrosine kinases shows an intramolecular interaction. Furthermore, the crystal structure of the Src family of tyrosine kinases reveals that the intramolecular interaction of SH3 and its ligand is the major determining factor keeping the kinase inactive. Thus, we propose an activation model that entails binding of Gqalpha to the TH-SH3 region, thereby disrupting the TH-SH3 intramolecular interaction and activating Btk.
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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.