ArticleThe EMBO journal2001
ShcA and Grb2 mediate polyoma middle T antigen-induced endothelial transformation and Gab1 tyrosine phosphorylation.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Membrane-bound Merkel cell polyomavirus middle T protein constitutively activates PLCγ1 signaling through Src-family kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- Role of EGF Receptor Regulatory Networks in the Host Response to Viral Infections.Frontiers in cellular and infection microbiology · 2021Review
- Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo.Oncogene · 2021Review
- Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation andmSphere · 2020Article
- Shc and the mechanotransduction of cellular anchorage and metastasis.Small GTPases · 2019Review
- Contributions of the RhoA guanine nucleotide exchange factor Net1 to polyoma middle T antigen-mediated mammary gland tumorigenesis and metastasis.Breast cancer research : BCR · 2018Article
- Insights into the Shc Family of Adaptor Proteins.Journal of molecular signaling · 2017Article
- A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling.Journal of virology · 2017Article
- p66Molecular and cellular biology · 2016Article
- Grb2 monomer-dimer equilibrium determines normal versus oncogenic function.Nature communications · 2015Article
- MET: a critical player in tumorigenesis and therapeutic target.Cold Spring Harbor perspectives in biology · 2013Review
- Generation of an immortalized murine brain microvascular endothelial cell line as an in vitro blood brain barrier model.Journal of visualized experiments : JoVE · 2012Article
- The fibronectin leucine-rich repeat transmembrane protein Flrt2 is required in the epicardium to promote heart morphogenesis.Development (Cambridge, England) · 2011Article
- Shp2 suppresses PyMT-induced transformation in mouse fibroblasts by inhibiting Stat3 activity.Virology · 2011Article
- Function, regulation and pathological roles of the Gab/DOS docking proteins.Cell communication and signaling : CCS · 2009Article
- Lessons in signaling and tumorigenesis from polyomavirus middle T antigen.Microbiology and molecular biology reviews : MMBR · 2009Review
- Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens.Seminars in cancer biology · 2009Review
- Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer.Virology · 2009Review
- New role for the protein tyrosine phosphatase DEP-1 in Akt activation and endothelial cell survival.Molecular and cellular biology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Middle T antigen (PymT) is the principal transforming component of polyomavirus, and rapidly induces hemangiomas in neonatal mice. PymT, a membrane-associated scaffold, recruits and activates Src family tyrosine kinases, and, once tyrosine phosphorylated, binds proteins with PTB and SH2 domains such as ShcA, phosphatidylinositol 3-kinase (PI3K) and phospholipase Cgamma-1 (PLCgamma-1). To explore the pathways required for endothelial transformation in vivo, we introduced PymT mutant forms into mice. PymT variants unable to bind PI3K and PLCgamma-1 directly induced hemangiomas similarly to wild type, but a mutant unable to bind ShcA was transformation compromised. Requirement for a ShcA PTB domain- binding site was suppressed by replacing this motif in PymT with YXN sequences, which bind the Grb2 SH2 domain upon phosphorylation. Surprisingly, PymT recruitment of ShcA and Grb2 correlated with PI3K activation. PymT mimics activated receptor tyrosine kinases by forming a ShcA-Grb2-Gab1 complex, thus inducing Gab1 tyrosine phosphorylation, which itself is associated with PI3K. Therefore, PymT activation of ShcA-Grb2 signaling is critical for endothelial transformation, and PymT can stimulate Grb2 signaling to both the MAP kinase and PI3K pathways.
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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.