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Based on my analysis of the GO-CAM model "gomodel:62d0afa500001077" (Insulin-like growth factor receptor signaling pathway 1 for Mouse) and the relevant documentation, I'll now provide a comprehensive review.

Review of GO-CAM Model: 62d0afa500001077 (Insulin-like growth factor receptor signaling pathway 1 - Mouse)

Overview

This model represents the insulin-like growth factor receptor (IGF1R) signaling pathway in mouse, sourced from human pathway models (gomodel:R-HSA-2404192 and gomodel:R-HSA-2428933). It illustrates the key molecular components and interactions in the IGF1R signaling cascade.

Biological Content Analysis

Pathway Components and Flow

The model correctly captures the core components of the IGF1R signaling pathway:

  1. Ligand-Receptor Interaction:
  2. IGF1 (Igf1) provides receptor ligand activity (GO:0048018)
  3. This directly positively regulates IGF1R (Igf1r) receptor activity (GO:0005010)

  4. The receptor binding involves ATP as input and ADP as output, correctly modeling the kinase activity

  5. Receptor Tyrosine Kinase Activity:

  6. IGF1R (Igf1r) has protein tyrosine kinase activity (GO:0004713)

  7. This directly positively regulates the adaptor protein SHC1 (Shc1)

  8. Adaptor Protein Recruitment and Function:

  9. SHC1 (Shc1) has transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068)
  10. SHC1 directly positively regulates GRB2 (Grb2)
  11. GRB2 (Grb2) has guanyl-nucleotide exchange factor adaptor activity (GO:0005091)

  12. GRB2 directly positively regulates SOS1 (Sos1)

  13. GEF Activity and RAS Activation:

  14. SOS1 (Sos1) has guanyl-nucleotide exchange factor activity (GO:0005085)
  15. SOS1 directly positively regulates HRAS (Hras)

  16. HRAS (Hras) has protein-membrane adaptor activity (GO:0043495)

  17. MAPK Cascade:

  18. HRAS activates RAF1 (Raf1) with MAP kinase kinase kinase activity (GO:0004709)
  19. RAF1 activates two MAP kinase kinases: MAP2K1 (Map2k1) and MAP2K2 (Map2k2) (GO:0004708)
  20. These activate the MAP kinases: MAPK1 (Mapk1) and MAPK3 (Mapk3) (GO:0004707)

Consistency with Literature

The model is well-supported by scientific literature: - Multiple references validate the IGF1-IGF1R interaction (e.g., PMID:32697974, PMID:35647546) - The tyrosine kinase activity of IGF1R is supported by PMID:9024787 - The adaptor roles of SHC1 and GRB2 in RTK signaling are documented extensively - The MAPK cascade activation downstream of IGF1R is consistent with established knowledge

GO-CAM Best Practices Assessment

Signaling Receptor Pathway Representation

✅ Ligand-Receptor Relationship: - Correctly models Igf1 as a protein ligand with receptor ligand activity - Uses "directly positively regulates" to connect ligand to receptor activity

✅ Receptor Activity: - Properly represents IGF1R with insulin-like growth factor receptor activity (GO:0005010) - Includes the ATP input and ADP output for the kinase activity - Appropriately models tyrosine kinase activity

✅ Adaptor Proteins: - Follows guidelines for molecular adaptor annotation - Uses appropriate molecular functions for adaptors (SHC1, GRB2) - Correctly employs the "directly positively regulates" relationship between adaptors

✅ Activity Flow: - Maintains proper causal direction of the pathway - Uses appropriate "directly positively regulates" predicates for causal relationships

✅ Biological Process Context: - All activities are appropriately placed within the insulin-like growth factor receptor signaling pathway (GO:0048009)

Areas for Enhancement

While the model is generally well-constructed, there are a few opportunities for improvement:

  1. Missing Evidence Codes: Two causal associations lack evidence:
  2. The causal association between MAP2K2 and MAPK3/MAPK1

  3. The causal association between MAP2K1 and MAPK3/MAPK1

  4. Downstream Effectors: The model could be extended to include:

  5. Transcription factor activation downstream of MAPK1/3

  6. The PI3K-AKT pathway branch of IGF1R signaling

  7. Negative Regulation: The model doesn't include negative regulators of the pathway (e.g., phosphatases)

Technical Quality

The model is technically well-constructed with: - Appropriate use of MGI identifiers for mouse gene products - Correct use of GO terms for molecular functions - Proper relationship types between activities - Good evidence coding with appropriate PMIDs

Conclusion

The GO-CAM model "gomodel:62d0afa500001077" is a high-quality representation of the IGF1R signaling pathway in mouse. It accurately captures the key molecular interactions and signaling flow from ligand binding to MAPK activation, following GO-CAM best practices for signaling pathway representation.

The model would benefit from adding the missing evidence codes for some causal associations and could be further enhanced by including additional branches of IGF1R signaling such as the PI3K-AKT pathway, as well as negative regulatory components.

Overall, this is a well-constructed model that provides a clear and accurate representation of IGF1R signaling suitable for research and educational purposes.