ArticleProceedings of the National Academy of Sciences of the United States of America2002
Gbeta gamma -independent constitutive association of Galpha s with SHP-1 and angiotensin II receptor AT2 is essential in AT2-mediated ITIM-independent activation of SHP-1.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 60 citations in OpenAlex.
- ATIP1 Is a Suppressor of Cardiac Hypertrophy and Modulates AT2-Dependent Signaling in Cardiac Myocytes.Cells · 2025Article
- The Angiotensin ATPharmacological reviews · 2022Review
- Pre-miRNA Hsa-Let-7a-2: a Novel Intracellular Partner of Angiotensin II Type 2 Receptor Negatively Regulating its Signals.International journal of biological sciences · 2022Article
- Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting.Frontiers in endocrinology · 2022Review
- Angiotensin II Type 2 Receptor: A Target for Protection Against Hypertension, Metabolic Dysfunction, and Organ Remodeling.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Potential of Renin-Angiotensin-Aldosterone System Modulations in Diabetic Kidney Disease: Old Players to New Hope!Reviews of physiology, biochemistry and pharmacology · 2021Review
- The Role of β-Arrestin Proteins in Organization of Signaling and Regulation of the AT1 Angiotensin Receptor.Frontiers in endocrinology · 2019Review
- Dimerization of ATCurrent hypertension reports · 2018Review
- International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].Pharmacological reviews · 2015Review
- Overexpression of angiotensin II type 2 receptor promotes apoptosis and impairs insulin secretion in rat insulinoma cells.Molecular and cellular biochemistry · 2015Article
- How does angiotensin AT(2) receptor activation help neuronal differentiation and improve neuronal pathological situations?Frontiers in endocrinology · 2012Article
- The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system.Molecular biology of the cell · 2011Article
- Angiotensin II activates AMPK for execution of apoptosis through energy-dependent and -independent mechanisms.American journal of physiology. Lung cellular and molecular physiology · 2011Article
- Src homology domain 2-containing protein-tyrosine phosphatase-1 (SHP-1) binds and dephosphorylates G(alpha)-interacting, vesicle-associated protein (GIV)/Girdin and attenuates the GIV-phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway.The Journal of biological chemistry · 2011Article
- Angiotensin II, a Neuropeptide at the Frontier between Endocrinology and Neuroscience: Is There a Link between the Angiotensin II Type 2 Receptor and Alzheimer's Disease?Frontiers in endocrinology · 2011Article
- The promyelocytic leukemia zinc finger (PLZF) protein exerts neuroprotective effects in neuronal cells and is dysregulated in experimental stroke.Brain pathology (Zurich, Switzerland) · 2011Article
- Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells.Journal of cell science · 2010Article
- Rab1 GTPase and dimerization in the cell surface expression of angiotensin II type 2 receptor.The Journal of pharmacology and experimental therapeutics · 2009Article
- Angiotensin II bi-directionally regulates cyclooxygenase-2 expression in intestinal epithelial cells.Molecular and cellular biochemistry · 2008Article
- Unconventional homologous internalization of the angiotensin II type-1 receptor induced by G-protein-independent signals.Hypertension (Dallas, Tex. : 1979) · 2005Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Conventional mode of activation of SH2 domain-containing phosphatase 1 (SHP-1) by a single transmembrane (TM) inhibitory receptor such as killer cell inhibitory receptor, Fcgamma receptor type IIb1, and paired Ig-like receptors of inhibitory types requires tyrosine phosphorylation of immunoreceptor tyrosine-based inhibitory (ITIM) motifs in the cytoplasmic domains of the inhibitory receptors. Contrary to this paradigm, AT(2), a G protein-coupled 7TM receptor that does not undergo tyrosine phosphorylation in response to angiotensin II (Ang II) stimulation, also activates SHP-1. Here we show that SHP-1 constitutively and physically associates with AT(2) receptor in transfected COS-7 cells. On stimulation by Ang II, SHP-1 becomes activated and dissociated from AT(2) receptor, independent of pertussis toxin. Cotransfection of transducin G(betagamma) inhibits SHP-1/AT(2) association and the SHP-1 activation, whereas cotransfection of C-terminal of beta-adrenergic receptor kinase, which abrogates G(betagamma) signaling, facilitates SHP-1 activation. Surprisingly, SHP-1/AT(2) association and the SHP-1 activation requires the presence of G(alphas) as shown by differential coimmunoprecipitation, dominant negative G(alphas), constitutively active G(alphas), and G(alpha) peptides. A mutant AT(2) receptor D141A-R142L that is inactive in G(alpha) protein activation constitutively associates with SHP-1 and activates it. Together, these results indicate that G(alphas) alone, rather than exclusively in the form of G(alphabetagamma) heterotrimer may facilitate signal transduction for G protein-coupled receptors, suggesting a novel mechanism distinct from the classic paradigm of heterotrimeric G proteins. The AT(2)-mediated ITIM-independent activation of SHP-1 that is distinct from the conventional mode of activation, may represent a general paradigm for activation of SHP-1/2-class tyrosine phosphatases by G protein-coupled receptors.
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