ArticleProceedings of the National Academy of Sciences of the United States of America1995
G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
24 citing papers in PubMed, 127 citations in OpenAlex.
- Endothelial protease-activated receptor 4: impotent or important?Frontiers in cardiovascular medicine · 2025Review
- Gi-coupled receptor activation potentiates Piezo2 currents via Gβγ.EMBO reports · 2020Article
- Membrane estradiol signaling in the brain.Frontiers in neuroendocrinology · 2009Review
- Chemokine signaling in cancer: one hump or two?Seminars in cancer biology · 2009Review
- Phosphorylation of TNF-alpha converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Platelet-activating factor increases pH(i) in bovine neutrophils through the PI3K-ERK1/2 pathway.British journal of pharmacology · 2004Article
- Ras activation in response to lysophosphatidic acid requires a permissive input from the epidermal growth factor receptor.The Biochemical journal · 2003Article
- A3 adenosine and CB1 receptors activate a PKC-sensitive Cl- current in human nonpigmented ciliary epithelial cells via a G beta gamma-coupled MAPK signaling pathway.British journal of pharmacology · 2003Article
- Review
- Signaling via Shc family adapter proteins.Oncogene · 2001Review
- Activation of extracellular signal-regulated protein kinases is associated with a sensitized locomotor response to D(2) dopamine receptor stimulation in unilateral 6-hydroxydopamine-lesioned rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000Article
- Gi-mediated translocation of GLUT4 is independent of p85/p110alpha and p110gamma phosphoinositide 3-kinases but might involve the activation of Akt kinase.The Biochemical journal · 2000Article
- Cloning and characterization of mPAL, a novel Shc SH2 domain-binding protein expressed in proliferating cells.Oncogene · 1999Article
- PI 3-kinase gamma and protein kinase C-zeta mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor.The EMBO journal · 1999Article
- Signal characteristics of G protein-transactivated EGF receptor.The EMBO journal · 1997Article
- Evidence for a requirement for both phospholipid and phosphotyrosine binding via the Shc phosphotyrosine-binding domain in vivo.Molecular and cellular biology · 1997Article
- Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation.Molecular and cellular biology · 1997Article
- Gi-mediated activation of the Ras/MAP kinase pathway involves a 100 kDa tyrosine-phosphorylated Grb2 SH3 binding protein, but not Src nor Shc.The EMBO journal · 1997Article
- Phosphatidylinositol 3-kinase is a negative regulator of cellular differentiation.The Journal of cell biology · 1997Article
- Dissociation of mitogen-activated protein kinase activation from p125 focal adhesion kinase tyrosine phosphorylation in Swiss 3T3 cells stimulated by bombesin, lysophosphatidic acid, and platelet-derived growth factor.Molecular biology of the cell · 1996Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, and an as-yet-unidentified tyrosine kinase. To investigate the mechanism of G beta gamma-stimulated p21ras activation, G beta gamma-mediated tyrosine phosphorylation was examined by overexpressing G beta gamma or alpha 2-C10 adrenergic receptors (ARs) that couple to Gi in COS-7 cells. Immunoprecipitation of phosphotyrosine-containing proteins revealed a 2- to 3-fold increase in the phosphorylation of two proteins of approximately 50 kDa (designated as p52) in G beta gamma-transfected cells or in alpha 2-C10 AR-transfected cells stimulated with the agonist UK-14304. The latter response was pertussis toxin sensitive. These proteins (p52) were also specifically immunoprecipitated with anti-Shc antibodies and comigrated with two Shc proteins, 46 and 52 kDa. The G beta gamma- or alpha 2-C10 AR-stimulated p52 (Shc) phosphorylation was inhibited by coexpression of the carboxyl terminus of beta-adrenergic receptor kinase (a G beta gamma-binding pleckstrin homology domain peptide) or by the tyrosine kinase inhibitors genistein and herbimycin A, but not by a dominant negative mutant of p21ras. Worthmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) inhibited phosphorylation of p52 (Shc), implying involvement of PI3K. These results suggest that G beta gamma-stimulated Shc phosphorylation represents an early step in the pathway leading to p21ras activation, similar to the mechanism utilized by growth factor tyrosine kinase receptors.
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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.