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Now let me analyze the GO-CAM model in detail based on the information I've gathered.

GO-CAM Model Review: gomodel:62e3212700000746 - Insulin-like growth factor receptor signaling pathway 3 (Mouse)

Model Overview

This GO-CAM model represents the insulin-like growth factor receptor signaling pathway in mouse (NCBITaxon:10090), sourced from several other models as noted in the comments. The model is currently in "production" status.

Components and Pathway Description

The model describes the following key components and activities in the IGF signaling pathway:

  1. Ligand-Receptor Interaction:
  2. Igf1 (MGI:MGI:96432) with receptor ligand activity (GO:0048018)
  3. Igf1r (MGI:MGI:96433) with insulin-like growth factor receptor activity (GO:0005010)

  4. The ligand (Igf1) directly positively regulates (RO:0002629) the receptor (Igf1r)

  5. Receptor Activation and Signaling:

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

  7. Activated Igf1r directly positively regulates (RO:0002629) the adaptor protein Irs1

  8. Adaptor Protein:

  9. Irs1 (MGI:MGI:99454) with transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068)

  10. Irs1 directly positively regulates (RO:0002629) the regulatory subunit of PI3K (Pik3r1)

  11. PI3K Activation:

  12. Pik3r1 (MGI:MGI:97583) with kinase activator activity (GO:0019209)
  13. Pik3r1 directly positively regulates (RO:0002629) the catalytic subunit of PI3K (Pik3ca)

  14. Pik3ca (MGI:MGI:1206581) with 1-phosphatidylinositol-3-kinase activity (GO:0016303)

  15. Downstream Signaling:

  16. Pik3ca directly positively regulates (RO:0002629) Pdpk1
  17. Pdpk1 (MGI:MGI:1338068) with 3-phosphoinositide-dependent protein kinase activity (GO:0004676)
  18. Pdpk1 directly positively regulates (RO:0002629) Akt1
  19. Akt1 (MGI:MGI:87986) with protein serine kinase activity (GO:0106310)

All of these activities are annotated as being part of the "insulin-like growth factor receptor signaling pathway" (GO:0048009).

Evidence Quality and Sources

The model is supported by multiple literature references, primarily: - PMID:11784871 - Study on PI3K subunit regulation in IGF-1 signaling - PMID:15116068 - PMID:12483226 - PMID:32439763 - PMID:7969452 - PMID:16642023 - PMID:23472139 - PMID:33377210

Evidence codes used include: - ECO:0000314 (direct assay evidence) - ECO:0000315 (mutant phenotype evidence) - ECO:0000316 (genetic interaction evidence) - ECO:0000266 (sequence orthology evidence)

QC Assessment

Strengths of the Model

  1. Comprehensive Pathway Representation: The model captures the key components and interactions of the canonical IGF-1 receptor signaling pathway, from ligand binding through PI3K activation to AKT activation.

  2. Strong Evidence Base: Multiple evidence types and publications support the model's assertions.

  3. Proper GO-CAM Conventions: The model follows the GO-CAM representation guidelines for signaling receptor pathways as outlined in the documentation, with proper relationship types between activities.

  4. Molecular Detail: The model correctly distinguishes between the different subunits of PI3K (regulatory and catalytic) and their respective activities.

Issues and Recommendations

  1. Missing Metabolites in Ligand-Receptor Interaction: While the model shows ATP → ADP in the receptor activity, this is a good practice for showing the molecular details of the kinase activity.

  2. Potentially Missing Outputs and Downstream Effects: The model doesn't include the downstream effects of Akt1 activation. According to the literature (PMID:11784871), Akt activation leads to antiapoptotic effects and phosphorylation of numerous substrates, which could be included for completeness.

  3. Missing Annotations: The biological context (cellular components) where each activity occurs is not specified, which could be added to improve the model's completeness.

  4. Pathway Termination: The pathway appears to end at Akt1 without indicating its downstream targets or biological outcomes. This makes it difficult to understand the ultimate biological effect of the pathway.

Consistency with Literature

The model is consistent with the scientific literature on IGF-1 signaling. PMID:11784871 supports the role of PI3K in IGF-1 signaling and the requirement for a balance between regulatory and catalytic subunits. The sequence of events (ligand binding → receptor activation → adaptor recruitment → PI3K activation → PDK1/AKT activation) is well-established in the literature.

Consistency with GO-CAM Best Practices

The model follows GO-CAM best practices for representing signaling pathways. According to the "Signaling receptor activity annotation guidelines" document:

  1. The proper relationship between ligand and receptor is represented
  2. The ligand (Igf1) has receptor ligand activity
  3. The receptor has insulin-like growth factor receptor activity
  4. The causal relation between ligand and receptor is "directly positively regulates"
  5. The receptor's input is properly represented as the effector protein it regulates (not its ligand)

Recommendations for Improvement

  1. Add Cellular Component Annotations: Include cellular component information for each activity (e.g., plasma membrane for receptor, cytosol for downstream components).

  2. Extend Downstream Effects: Include key downstream substrates of Akt1 to show the biological outcomes of the pathway activation.

  3. Include Negative Regulators: Consider adding negative regulators of the pathway such as phosphatases (e.g., PTEN) which are mentioned in the literature review (PMID:11784871).

  4. Add Additional Cross-Regulation: Include cross-talk with other signaling pathways where relevant.

  5. Include Feedback Mechanisms: IGF signaling typically involves feedback regulation which could be represented in the model.

Conclusion

The GO-CAM model gomodel:62e3212700000746 provides a solid representation of the insulin-like growth factor receptor signaling pathway in mouse. It accurately captures the core components of the pathway with appropriate molecular functions and causal relationships. The model follows GO-CAM best practices and is supported by strong evidence from the literature.

While the model could be expanded to include more downstream effects and regulatory mechanisms, it serves as a valuable resource for understanding the fundamental components and organization of IGF-1 receptor signaling.