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61e0e55600000239 Epidermal growth factor receptor signaling pathway 10 Mouse

Based on the information gathered, I will now review the GO-CAM model gomodel:61e0e55600000239 "Epidermal growth factor receptor signaling pathway 10 (Mouse)".

GO-CAM Review: gomodel:61e0e55600000239

Summary of the Model

This GO-CAM model represents the Epidermal Growth Factor Receptor (EGFR) signaling pathway in mouse, focusing on a specific signaling cascade from the ligand TGF-alpha through EGFR and downstream adaptor proteins.

Model Components

The model consists of the following key molecular functions and their associated gene products:

  1. TGF-alpha (MGI:MGI:98724) - Performs "receptor ligand activity" (GO:0048018) in the extracellular space (GO:0005615).

  2. EGFR (MGI:MGI:95294) - Has dual functionalities in the model:

  3. Performs "epidermal growth factor receptor activity" (GO:0005006) in the plasma membrane (GO:0005886)

  4. Performs "protein tyrosine kinase activity" (GO:0004713) in the cell cortex (GO:0005938)

  5. Grb2 (MGI:MGI:95805) - Performs "transmembrane receptor protein tyrosine kinase adaptor activity" (GO:0005068) in the cell cortex (GO:0005938)

  6. Gab1 (MGI:MGI:108088) - Performs "signaling adaptor activity" (GO:0035591) in the cell cortex (GO:0005938)

  7. Ptpn11/SHP2 (MGI:MGI:99511) - Performs "non-membrane spanning protein tyrosine phosphatase activity" (GO:0004726) in the cytosol (GO:0005829)

Causal Relationships

The model illustrates a signal transduction cascade with the following causal relationships: 1. TGF-alpha → directly positively regulates → EGFR receptor activity 2. EGFR receptor activity → directly positively regulates → Grb2 adaptor activity 3. Grb2 → provides input for → EGFR kinase activity 4. EGFR kinase activity → directly positively regulates → Gab1 adaptor activity 5. Gab1 → directly positively regulates → Ptpn11/SHP2 phosphatase activity

Evidence Support

The model is supported by several publications, including PMID:7678348, PMID:17881575, and PMID:9890893, among others.

Review Assessment

Biological Content Consistency

The represented EGFR signaling pathway aligns well with established knowledge of this pathway: 1. The model correctly shows TGF-alpha as a ligand for EGFR, activating its receptor function 2. It accurately represents EGFR's dual roles as a receptor and a kinase 3. The adapter protein cascade involving Grb2, Gab1, and the phosphatase Ptpn11/SHP2 is consistent with the literature on EGFR signaling

GO-CAM Best Practices Compliance

✓ Signaling Receptor Activity Annotation:

The model follows the guidelines for annotating signaling receptor activity: - TGF-alpha is correctly annotated with receptor ligand activity in the extracellular space - EGFR is annotated with receptor activity in the plasma membrane - The causal relationship between ligand and receptor uses "directly positively regulates"

✓ Activity Flow:

The activity flow in the pathway is logical and follows the expected pattern of EGFR signaling: 1. Ligand binding → receptor activation → adaptor recruitment → signal transduction

✓ Cellular Compartments:

The cellular locations are properly specified: - TGF-alpha in extracellular space - EGFR in plasma membrane and cell cortex - Adaptor proteins in appropriate cellular locations

✓ Evidence:

Each activity and relationship is backed by appropriate evidence codes and literature references.

Minor Areas for Improvement

  1. EGFR Compartmentalization: While the model shows EGFR kinase activity in the cell cortex, it may be worth noting that EGFR can also undergo endocytosis and signaling from endosomes. This additional compartmentalization could potentially be included in a more comprehensive model.

  2. Downstream Effectors: The current model ends with Ptpn11/SHP2 activity. In the broader EGFR pathway, SHP2 typically leads to activation of the Ras-MAPK pathway. Extending the model to include these downstream effectors would provide a more complete representation of EGFR signaling.

  3. Cross-talk with Other Pathways: EGFR signaling often intersects with other signaling pathways. While this model focuses on one specific branch, acknowledging these connections could enhance its biological relevance.

Conclusion

The GO-CAM model gomodel:61e0e55600000239 is a well-constructed representation of the EGFR signaling pathway in mouse. It adheres to GO-CAM curation best practices and accurately represents the biology of EGFR signaling as documented in the literature. The causal relationships between molecular functions are clearly defined, and each activity is properly contextualized with cellular locations and biological process involvement.

The model could potentially be expanded to include additional downstream events or cross-talk with other pathways, but as a focused representation of the core EGFR signaling cascade, it is accurate and valuable.

Overall, this model can be considered a high-quality contribution to the GO-CAM database that effectively captures key aspects of EGFR signaling.