ArticleThe Journal of cell biology2008
The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1.
Article in The Journal of cell biology, 2008. 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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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Lipid-driven Src self-association modulates its transformation capacity.Life science alliance · 2025Article
- CSK-mediated signalling by integrins in cancer.Frontiers in cell and developmental biology · 2023Review
- Mechanical Control of Cell Migration by the Metastasis Suppressor Tetraspanin CD82/KAI1.Cells · 2021Article
- Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis.Cancers · 2020Review
- GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells.Stem cells international · 2018Article
- Review
- ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells.Journal of virology · 2015Article
- YES oncogenic activity is specified by its SH4 domain and regulates RAS/MAPK signaling in colon carcinoma cells.American journal of cancer research · 2015Article
- PAG--a multipurpose transmembrane adaptor protein.Oncogene · 2014Review
- How Do Gangliosides Regulate RTKs Signaling?Cells · 2013Article
- Oncogenic signaling by tyrosine kinases of the SRC family in advanced colorectal cancer.American journal of cancer research · 2012Article
- A HIF-regulated VHL-PTP1B-Src signaling axis identifies a therapeutic target in renal cell carcinoma.Science translational medicine · 2011Article
- Article
- Src family tyrosine kinases-driven colon cancer cell invasion is induced by Csk membrane delocalization.Oncogene · 2010Article
- The transmembrane protein CBP plays a role in transiently anchoring small clusters of Thy-1, a GPI-anchored protein, to the cytoskeleton.Journal of cell science · 2009Article
- Endocytosis and spatial restriction of cell signaling.Molecular oncology · 2009Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spatial regulation is an important feature of signal specificity elicited by cytoplasmic tyrosine kinases of the Src family (SRC family protein tyrosine kinases [SFK]). Cholesterol-enriched membrane domains, such as caveolae, regulate association of SFK with the platelet-derived growth factor receptor (PDGFR), which is needed for kinase activation and mitogenic signaling. PAG, a ubiquitously expressed member of the transmembrane adaptor protein family, is known to negatively regulate SFK signaling though binding to Csk. We report that PAG modulates PDGFR levels in caveolae and SFK mitogenic signaling through a Csk-independent mechanism. Regulation of SFK mitogenic activity by PAG requires the first N-terminal 97 aa (PAG-N), which include the extracellular and transmembrane domains, palmitoylation sites, and a short cytoplasmic sequence. We also show that PAG-N increases ganglioside GM1 levels at the cell surface and, thus, displaces PDGFR from caveolae, a process that requires the ganglioside-specific sialidase Neu-3. In conclusion, PAG regulates PDGFR membrane partitioning and SFK mitogenic signaling by modulating GM1 levels within caveolae independently from Csk.
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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.