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Now, I'll review the GO-CAM model with ID 6197061700000593 based on the information I've gathered.

Review of GO-CAM Model 6197061700000593: ERBB2-EGFR signaling pathway 1 (Mouse)

Overview of the Model

This model represents the ERBB2-EGFR signaling pathway in mouse (NCBITaxon:10090) and includes activities related to four key proteins: - EGFR (Epidermal Growth Factor Receptor, MGI:MGI:95294) - ERBB2 (MGI:MGI:95410) - HB-EGF (Heparin-binding EGF-like growth factor, MGI:MGI:96070) - ADAM17 (A disintegrin and metalloprotease 17, MGI:MGI:1096335)

Biological Accuracy

Overall, the model accurately captures key aspects of the ERBB2-EGFR signaling pathway based on the literature:

  1. The model correctly represents HB-EGF as a ligand that activates EGFR
  2. ADAM17 is correctly positioned as processing the HB-EGF precursor
  3. EGFR activation leads to ERBB2 kinase activity, consistent with the well-established EGFR-ERBB2 heterodimerization

The connections between components reflect established knowledge about this pathway, with causal relationships that align with the biological mechanisms described in the literature (PMID:21946538, PMID:14993236, PMID:16357442, PMID:19029950).

GO-CAM Best Practices Assessment

Strengths:

  1. Proper use of causal relations:
  2. The model uses RO:0002304 (causally upstream of, positive effect) for ADAM17's processing of HB-EGF

  3. RO:0002629 (directly positively regulates) is appropriately used for ligand-receptor and receptor-receptor interactions

  4. Appropriate cellular location annotations:

  5. Activities properly annotated with cellular locations (GO:0005886 for plasma membrane, GO:0005615 for extracellular space)

  6. Clear molecular functions:

  7. Each protein is assigned appropriate molecular functions:

    • EGFR: GO:0005006 (epidermal growth factor receptor activity)
    • ERBB2: GO:0004713 (protein tyrosine kinase activity)
    • HB-EGF: GO:0048018 (receptor ligand activity)
    • ADAM17: GO:0004222 (metalloendopeptidase activity)

  8. Strong evidence support:

  9. Each activity and relationship has appropriate evidence codes and literature references

  10. Uses a mix of direct assay (ECO:0000314), mutant phenotype (ECO:0000315), and genetic interaction (ECO:0000316) evidence

  11. Biological process annotations:

  12. All activities are part of GO:0038134 (ERBB2-EGFR signaling pathway), providing context
  13. ADAM17 activity is correctly placed within GO:0140448 (signaling receptor ligand precursor processing)

Areas for Improvement:

  1. Complex representation:

  2. The model doesn't explicitly represent the EGFR-ERBB2 heterodimer complex. According to GO-CAM best practices for complex annotation, the heterodimer formation could be more explicitly represented.

  3. Downstream effects:

  4. The model ends with ERBB2 kinase activity but doesn't include downstream effects such as MAPK or PI3K/Akt activation, which are major effectors of EGFR-ERBB2 signaling as identified in the literature (PMID:21946538).

  5. Feedback regulation:

  6. No representation of negative feedback mechanisms that are known to regulate EGFR signaling.
  1. Heterodimer representation:

  2. Consider explicitly representing the EGFR-ERBB2 heterodimer following the GO-CAM complex annotation guidelines

  3. Expand downstream signaling:

  4. Consider adding key downstream events such as PI3K/Akt and MAPK pathway activation, which are established consequences of EGFR-ERBB2 signaling

  5. Include receptor trafficking:

  6. Consider representing receptor internalization processes, which are important regulatory mechanisms for EGFR signaling

  7. Add additional context:

  8. The function of this pathway in specific biological processes (beyond just being part of GO:0038134) could provide additional context

Conclusion

GO-CAM model 6197061700000593 provides an accurate representation of the core ERBB2-EGFR signaling pathway, with proper annotation of molecular functions, cellular locations, and causal relationships. The model is well-supported by evidence from the literature. While the current model effectively captures the essential components of this pathway, expanding it to include heterodimer formation, downstream signaling events, and regulatory mechanisms would provide a more comprehensive representation of ERBB2-EGFR signaling.

The model follows GO-CAM best practices for the most part, with appropriate use of relationships and evidence codes. The suggestions for improvement would enhance the biological completeness rather than correcting any significant errors in the existing model.