EGF Receptor Downregulation by CBL Pathway

Preferred Label : EGF Receptor Downregulation by CBL Pathway;

NCIt related terms : CBL mediated ligand-induced downregulation of EGF receptors;

Alternative definition : BIOCARTA: As with many cell-surface receptors, activation of the EGF receptor can result in receptor internalization through receptor-mediated endocytosis, desensitizing further receptor signaling. This process requires clathrin and occurs in clathrin-coated pits, which pinch off from the plasma membrane to form vesicles that move to the early endosome. From the early endosome, receptors can either be recycled back to the cell surface, or they can move through the late endosome to the lysosome for proteolytic degradation. The sorting of receptors in the early endosome for degradation requires the tyrosine kinase activity of activated growth factor receptor and involves ubiquitination of the receptor. Targeting of receptors for degradation requires members of the Cbl gene family. Cbl proteins bind to tyrosine phosphorylated EGF receptor, and are E3 ubiquitination ligases that label receptor for degradation. Cbl also recruits Cin85 to the receptor complex, and blocking Cin85 interaction blocks receptor internalization and degradation. Endophilins are also a member of this receptor-bound protein complex. In its role as a ubiquitin ligase and docking protein, Cbl desensitizes EGF signaling and also opposes cellular proliferation induced by EGF. EGF activation also appears to activate the tyrosine kinase Src, which phosphorylates Cbl, and helps to activate the ubiquitination and degradation of EGF receptor. PKC activation and threonine phosphorylation of the EGF receptor can induce heterologous receptor internalization, but opposes Cbl-mediated receptor degradation. PKC phosphorylated receptors are sorted for recycling to the cell surface, and directed away from the late endosome and proteasome. Other growth factor receptors are regulated in a similar manner, including the PDGF receptor, HGF receptor and the CSF-1 receptor, indicating that this is a fairly general regulatory mechanism. The importance of Cbl in the down-regulation of growth factor signaling means that it will have an important role in cellular transformation and the development and treatment of cancer. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_cblPathway;

Details

Origin ID

C39016;

UMLS CUI

C1512119;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- E3 Ubiquitin-Protein Ligase CBL [NCIt concept]
- Endoglin [NCIt concept]
- Epidermal Growth Factor [NCIt concept]
- Epidermal Growth Factor Receptor [NCIt concept]
- Growth Factor Receptor-Bound Protein 2 [NCIt concept]
- Hepatocyte Growth Factor Receptor [NCIt concept]
- Macrophage Colony-Stimulating Factor 1 Receptor [NCIt concept]
- Platelet-Derived Growth Factor Receptor Alpha [NCIt concept]
- Protein Kinase C Alpha Type [NCIt concept]
- Proto-Oncogene Tyrosine-Protein Kinase Src [NCIt concept]
- SH3 Domain-Containing Kinase-Binding Protein 1 [NCIt concept]
pathway_has_gene_element
- CBL wt Allele [NCIt concept]
- CSF1R wt Allele [NCIt concept]
- EGF wt Allele [NCIt concept]
- EGFR wt Allele [NCIt concept]
- ENG wt Allele [NCIt concept]
- GRB2 wt Allele [NCIt concept]
- MET wt Allele [NCIt concept]
- PDGFRA wt Allele [NCIt concept]
- PRKCA wt Allele [NCIt concept]
- SH3KBP1 wt Allele [NCIt concept]
- SRC wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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