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62d0afa500000472 Insulin receptor signalling pathway 3 Mouse

Now that I have gathered all the necessary information, I'll review the GO-CAM model gomodel:62d0afa500000472 "Insulin receptor signalling pathway 3 (Mouse)".

Review of GO-CAM Model: Insulin receptor signalling pathway 3 (Mouse)

Model Overview

The model represents the insulin receptor signaling pathway in mouse (NCBITaxon:10090). It includes 10 activities encompassing: - Insulin ligands (Ins1 and Ins2) - Insulin receptor (Insr) - Adaptor proteins (Irs1, Irs2) - Signal transduction components (Grb2, Sos1, Sos2, Hras)

Biological Content Assessment

  1. Pathway Representation:
  2. The model correctly captures the key components of insulin receptor signaling
  3. The pathway starts with insulin ligands (Ins1, Ins2) activating the insulin receptor (Insr)
  4. The activated receptor engages in tyrosine kinase activity and signals through adaptor proteins (Irs1, Irs2)

  5. This leads to activation of the Ras-MAPK pathway via Grb2, Sos1/Sos2, and Hras

  6. Causal Flow:

  7. The causal associations using RO:0002629 (directly positively regulates) are appropriate for this signaling pathway

  8. The flow is logical and consistent with known insulin signaling:

    • Insulin ligands → Insulin receptor → Receptor tyrosine kinase activity → Adaptor proteins → Downstream signaling components

  9. Evidence:

  10. Most activities and causal associations are supported by primary literature references (e.g., PMID:8649419, PMID:8448209, PMID:23886629)
  11. Evidence codes are appropriate (e.g., ECO:0000314 for direct assay evidence, ECO:0000315 for mutant phenotype evidence)

Compliance with GO-CAM Best Practices

  1. Signaling Receptor Annotation Guidelines:
  2. The model correctly represents insulin (Ins1, Ins2) with receptor ligand activity (GO:0048018)
  3. The insulin receptor (Insr) is properly annotated with insulin receptor activity (GO:0005009)
  4. The causal relationship between ligand and receptor is correctly modeled using the "directly positively regulates" predicate

  5. The tyrosine kinase activity of the receptor is appropriately represented as the next step in the pathway

  6. Molecular Adaptor Annotation:

  7. Grb2 is correctly annotated with guanyl-nucleotide exchange factor adaptor activity (GO:0005091)
  8. The adaptor proteins Irs1 and Irs2 are correctly annotated with transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068)

  9. The causal relationships between activities are properly modeled

  10. Activity Connections:

  11. All activities are properly connected with causal relationships that follow the expected biological progression
  12. The insulin receptor signaling pathway process (GO:0008286) provides the unifying biological context for all activities

Issues/Concerns

I've identified a few potential issues in the model:

  1. Missing Cellular Component Annotations:
  2. Unlike the comparison model (gomodel:62b4ffe300004795), this model lacks cellular component annotations (e.g., plasma membrane for insulin receptor, extracellular space for insulin)

  3. According to best practices, cellular component annotations help specify where activities occur

  4. Evidence Missing for Some Causal Associations:

  5. Some causal associations lack evidence annotations, particularly:

    • The connection between Insr protein tyrosine kinase activity (62d0afa500000608) and Irs1 adaptor activity (62d0afa500000610)
    • The connection between Irs2 adaptor activity (62d0afa500000616) and Grb2 adaptor activity (62d0afa500000612)

  6. Downstream Signaling Pathway:

  7. Compared to the example model (62b4ffe300004795), this model stops at Hras/protein-membrane adaptor activity and doesn't include the downstream MAP kinase cascade (MAPK1, MAPK3)

  8. However, this may be intentional as the focus might be on the initial steps of insulin signaling

  9. Limited Biochemical Depth:

  10. The model would benefit from additional annotations related to the specific interactions between components
  11. Some of the molecular details of insulin receptor autophosphorylation and adaptor protein binding are not explicitly represented

Conclusion

Overall, this is a well-constructed model that accurately represents the insulin receptor signaling pathway in mouse. It follows most GO-CAM best practices for signaling pathway annotation, with proper use of molecular functions, biological processes, and causal relationships.

Strengths: - Correctly represents insulin receptor signaling components and their relationships - Uses appropriate molecular function terms and causal associations - Well-supported by primary literature evidence

Recommendations for improvement: 1. Add cellular component annotations for relevant activities (e.g., plasma membrane for receptor, extracellular space for ligands) 2. Provide evidence for all causal associations 3. Consider extending the model to include downstream signaling components (MAP kinase cascade) 4. Add annotations to capture more details of molecular interactions where relevant

The model is consistent with biological knowledge about insulin receptor signaling and follows the GO-CAM best practices, making it a valid representation of this important signaling pathway.