ArticleMolecular and cellular biology2012
Intersectin 1 enhances Cbl ubiquitylation of epidermal growth factor receptor through regulation of Sprouty2-Cbl interaction.
Article in Molecular and cellular biology, 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- RAPDOR: Using Jensen-Shannon Distance for the computational analysis of complex proteomics datasets.Nature communications · 2025Article
- PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability.Oncogenesis · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions.Molecular systems biology · 2020Article
- Cockayne syndrome group A and B proteins function in rRNA transcription through nucleolin regulation.Nucleic acids research · 2020Article
- PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Intersectin-s interaction with DENND2B facilitates recycling of epidermal growth factor receptor.EMBO reports · 2017Article
- Intersectin-1s deficiency in pulmonary pathogenesis.Respiratory research · 2017Review
- Endocytosis and membrane receptor internalization: implication of F-BAR protein Carom.Frontiers in bioscience (Landmark edition) · 2017Review
- Intersectin scaffold proteins and their role in cell signaling and endocytosis.Biochimica et biophysica acta. Molecular cell research · 2017Review
- Phosphatidylinositol 3-kinase, class 2 beta (PI3KC2β) isoform contributes to neuroblastoma tumorigenesis.Cancer letters · 2015Article
- Receptor tyrosine kinase ubiquitylation involves the dynamic regulation of Cbl-Spry2 by intersectin 1 and the Shp2 tyrosine phosphatase.Molecular and cellular biology · 2014Article
- Cytoplasmic retention of a nucleocytoplasmic protein TBC1D3 by microtubule network is required for enhanced EGFR signaling.PloS one · 2014Article
- Emerging roles for intersectin (ITSN) in regulating signaling and disease pathways.International journal of molecular sciences · 2013Review
- Intersectin (ITSN) family of scaffolds function as molecular hubs in protein interaction networks.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Ubiquitylation of receptor tyrosine kinases plays a critical role in regulating the trafficking and lysosomal degradation of these important signaling molecules. We identified the multidomain scaffolding protein intersectin 1 (ITSN1) as an important regulator of this process (N. P. Martin et al., Mol. Pharmacol. 70:1463-1653, 2006) ITSN1 stimulates ubiquitylation of the epidermal growth factor receptor (EGFR) through enhancing the activity of the Cbl E3 ubiquitin ligase. However, the precise mechanism through which ITSN1 enhances Cbl activity was unclear. In this study, we found that ITSN1 enhances Cbl activity through disrupting the interaction of Cbl with the Sprouty2 (Spry2) inhibitory protein. We demonstrate that ITSN1 binds Pro-rich regions in both Cbl and Spry2 and that interaction of ITSN1 with Spry2 disrupts Spry2-Cbl interaction, resulting in enhanced ubiquitylation of the EGFR. Disruption of ITSN1 binding to Spry2 through point mutation of the Pro-rich ITSN1 binding site in Spry2 results in enhanced Cbl-Spry2 interaction and inhibition of receptor ubiquitylation. This study demonstrates that ITSN1 enhances Cbl activity by modulating the interaction of Cbl with Spry2. In addition, our results reveal a new level of complexity in the regulation of Cbl through the interaction with ITSN1 and Spry2.
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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.