ArticleThe Journal of biological chemistry2009
Noonan syndrome/leukemia-associated gain-of-function mutations in SHP-2 phosphatase (PTPN11) enhance cell migration and angiogenesis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- [Diagnostic and therapeutic perspectives in RASopathies].Magyar onkologia · 2024Review
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- Anterior Uveitis and Coats Disease in a 16-Year-Old Girl with Noonan Syndrome-A Case Report.Children (Basel, Switzerland) · 2023Article
- Genetic and Proteomic Contributions to the Pathophysiology of Moyamoya Angiopathy and Related Vascular Diseases.The application of clinical genetics · 2021Review
- SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs.Frontiers in physiology · 2020Article
- Identifying Candidate Druggable Targets in Canine Cancer Cell Lines Using Whole-Exome Sequencing.Molecular cancer therapeutics · 2019Article
- Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.Genes · 2017Article
- RASopathies: unraveling mechanisms with animal models.Disease models & mechanisms · 2015Review
- Conditional Knockout of Src Homology 2 Domain-containing Protein Tyrosine Phosphatase-2 in Myeloid Cells Attenuates Renal Fibrosis after Unilateral Ureter Obstruction.Chinese medical journal · 2015Article
- Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis.Human molecular genetics · 2014Article
- The anti-inflammatory compound BAY-11-7082 is a potent inhibitor of protein tyrosine phosphatases.The FEBS journal · 2013Article
- Protein tyrosine phosphatase expression profile of rheumatoid arthritis fibroblast-like synoviocytes: a novel role of SH2 domain-containing phosphatase 2 as a modulator of invasion and survival.Arthritis and rheumatism · 2013Article
- Article
- Protein Tyrosine Phosphatase SHP-2 (PTPN11) in Hematopoiesis and Leukemogenesis.Journal of signal transduction · 2011Article
- Article
- Gab1 mediates hepatocyte growth factor-stimulated mitogenicity and morphogenesis in multipotent myeloid cells.Journal of cellular biochemistry · 2010Article
- SHP-2 phosphatase activity is required for PECAM-1-dependent cell motility.American journal of physiology. Cell physiology · 2010Article
- Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling.Molecular and cellular biology · 2010Article
- GNAI2 and regulators of G protein signaling as a potential Noonan syndrome mechanism.Medical hypotheses · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in SHP-2 phosphatase (PTPN11) that cause hyperactivation of its catalytic activity have been identified in Noonan syndrome and various childhood leukemias. Recent studies suggest that the gain-of-function (GOF) mutations of SHP-2 play a causal role in the pathogenesis of these diseases. However, the molecular mechanisms by which GOF mutations of SHP-2 induce these phenotypes are not fully understood. Here, we show that GOF mutations in SHP-2, such as E76K and D61G, drastically increase spreading and migration of various cell types, including hematopoietic cells, endothelial cells, and fibroblasts. More importantly, in vivo angiogenesis in SHP-2 D61G knock-in mice is also enhanced. Mechanistic studies suggest that the increased cell migration is attributed to the enhanced beta1 integrin outside-in signaling. In response to beta1 integrin cross-linking or fibronectin stimulation, activation of ERK and Akt kinases is greatly increased by SHP-2 GOF mutations. Also, integrin-induced activation of RhoA and Rac1 GTPases is elevated. Interestingly, mutant cells with the SHP-2 GOF mutation (D61G) are more sensitive than wild-type cells to the suppression of cell motility by inhibition of these pathways. Collectively, these studies reaffirm the positive role of SHP-2 phosphatase in cell motility and suggest a new mechanism by which SHP-2 GOF mutations contribute to diseases.
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