ArticleThe Journal of biological chemistry2012
Src homology 2 domain-containing phosphatase 2 (Shp2) is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex and is inhibited by protein kinase A (PKA) under pathological hypertrophic conditions in the heart.
Article in The Journal of biological chemistry, 2012. 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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16 citing papers in PubMed, 18 citations in OpenAlex.
- Hypoxia induced DNMT3B and SHP2 signaling promoted HCC via suppressing P53 and MYH11 protein expression.Frontiers in oncology · 2026Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- SHP099-containing multi-targeting hydrogel promotes rapid skin reconstruction through modulating a variety of cells.Frontiers in bioengineering and biotechnology · 2025Article
- Review
- Cardiac function modulation depends on the A-kinase anchoring protein complex.Journal of cellular and molecular medicine · 2019Review
- CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway.Molecular and cellular biology · 2017Article
- Antidepressant Activity ofInternational journal of preventive medicine · 2016Article
- Repeated Mu-Opioid Exposure Induces a Novel Form of the Hyperalgesic Priming Model for Transition to Chronic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Protein Kinase A (PKA) Phosphorylation of Shp2 Protein Inhibits Its Phosphatase Activity and Modulates Ligand Specificity.The Journal of biological chemistry · 2015Article
- UCR1C is a novel activator of phosphodiesterase 4 (PDE4) long isoforms and attenuates cardiomyocyte hypertrophy.Cellular signalling · 2015Article
- The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.The Biochemical journal · 2014Article
- Structural insights into the activation of the RhoA GTPase by the lymphoid blast crisis (Lbc) oncoprotein.The Journal of biological chemistry · 2014Article
- Receptor tyrosine kinase ubiquitylation involves the dynamic regulation of Cbl-Spry2 by intersectin 1 and the Shp2 tyrosine phosphatase.Molecular and cellular biology · 2014Article
- The C-terminus of the long AKAP13 isoform (AKAP-Lbc) is critical for development of compensatory cardiac hypertrophy.Journal of molecular and cellular cardiology · 2014Article
- Article
- Molecular crosstalk between insulin-like growth factors and follicle-stimulating hormone in the regulation of granulosa cell function.Reproductive medicine and biologyReview
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAKAP-Lbc is a scaffold protein that coordinates cardiac hypertrophic signaling.
resultsAKAP-Lbc interacts with Shp2, facilitating its regulation by PKA.
conclusionAKAP-Lbc integrates PKA and Shp2 signaling in the heart. Under pathological hypertrophic conditions Shp2 is phosphorylated by PKA, and phosphatase activity is inhibited. SIGNIFICANCE: Inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote pathological cardiac hypertrophy. Pathological cardiac hypertrophy (an increase in cardiac mass resulting from stress-induced cardiac myocyte growth) is a major factor underlying heart failure. Our results identify a novel mechanism of Shp2 inhibition that may promote cardiac hypertrophy. We demonstrate that the tyrosine phosphatase, Shp2, is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex. AKAP-Lbc facilitates PKA phosphorylation of Shp2, which inhibits its protein-tyrosine phosphatase activity. Given the important cardiac roles of both AKAP-Lbc and Shp2, we investigated the AKAP-Lbc-Shp2 interaction in the heart. AKAP-Lbc-tethered PKA is implicated in cardiac hypertrophic signaling; however, mechanism of PKA action is unknown. Mutations resulting in loss of Shp2 catalytic activity are also associated with cardiac hypertrophy and congenital heart defects. Our data indicate that AKAP-Lbc integrates PKA and Shp2 signaling in the heart and that AKAP-Lbc-associated Shp2 activity is reduced in hypertrophic hearts in response to chronic β-adrenergic stimulation and PKA activation. Thus, while induction of cardiac hypertrophy is a multifaceted process, inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote compensatory cardiac hypertrophy.
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