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61b2b68300000617 ERBB2 ERBB3 receptor signaling pathway involved in myelination 1 Mouse

Now, let me review and analyze the GO-CAM model based on the retrieved information:

GO-CAM Model Review: ERBB2-ERBB3 receptor signaling pathway involved in myelination 1 (Mouse)

Model ID: gomodel:61b2b68300000617

Overview

This model represents the ERBB2-ERBB3 receptor signaling pathway involved in myelination in mouse. It demonstrates the signaling cascade from the Neuregulin-1 (NRG1) ligand activating the ERBB2-ERBB3 receptor complex, leading to subsequent downstream MAPK signaling events.

Structure and Content Assessment

1. Signaling Pathway Flow

The model correctly shows a linear flow of signal transduction from: - Nrg1 (ligand) → Erbb3 (receptor) → Erbb2 (co-receptor) → Grb2 (adaptor) → Sos1 (GEF) → Hras → Raf1 → Map2k1/2 → Mapk1/3

This is consistent with the canonical ERBB receptor signaling pathway leading to MAPK cascade activation.

2. Molecular Functions & Annotations

  • Ligand: Nrg1 (MGI:MGI:96083) is appropriately annotated with "receptor ligand activity" (GO:0048018) occurring in "extracellular space" (GO:0005615)
  • Receptors: Erbb2 and Erbb3 are correctly annotated, with Erbb3 having "neuregulin receptor activity" (GO:0038131) and Erbb2 having "protein tyrosine kinase activity" (GO:0004713), both occurring in "plasma membrane" (GO:0005886)
  • Adaptor proteins: Grb2 is correctly annotated with "transmembrane receptor protein tyrosine kinase adaptor activity" (GO:0005068)
  • GEF: Sos1 has "guanyl-nucleotide exchange factor activity" (GO:0005085)
  • MAPK cascade components: All components (Hras, Raf1, Map2k1/2, Mapk1/3) have appropriate kinase activities located in appropriate cellular compartments

3. Causal Relationships

The model correctly uses "directly positively regulates" (RO:0002629) for causal relationships between activities, showing the signal flow through the pathway.

Compliance with GO-CAM Best Practices

Signaling Receptor Annotation

The model follows the signaling receptor annotation guidelines: - The ligand (Nrg1) has receptor ligand activity - The receptors (Erbb2/3) are correctly located in plasma membrane - Causal relations use appropriate directional regulation relationships

Complexes Annotation

While not explicitly using a complex ID, the model represents the ERBB2-ERBB3 receptor complex appropriately by modeling each subunit separately with their respective activities, which is consistent with the "subunit that carries the molecular activity is known" guideline.

Evidence Quality

  • The model uses appropriate evidence codes:
  • ECO:0000266 (sequence orthology evidence)
  • ECO:0000315 (mutant phenotype evidence)
  • ECO:0000314 (direct assay evidence)
  • The model includes relevant PMIDs as references for assertions

Biological Accuracy Assessment

The model accurately represents the ERBB2-ERBB3 signaling pathway: - NRG1 is a known activator of ERBB2-ERBB3 heterodimers - The subsequent MAPK cascade activation is biologically accurate - The model correctly shows that the signal transduction leads to myelination process, which is a known biological role of ERBB2-ERBB3 signaling in Schwann cells

Improvement Opportunities

  1. Missing Information: The model doesn't explicitly connect to the final myelination process (GO:0042552) - this could be added to show the terminal biological outcome

  2. Evidence Support: Some occurs_in relationships lack evidence sources

  3. Redundancy: There's some redundancy in the Map2k1 and Map2k2 pathways - they both activate the same downstream targets (Mapk1 and Mapk3) which could potentially be simplified

  4. Part_of Annotations: All activities are part of the ERBB2-ERBB3 signaling pathway (GO:0038133), but some downstream activities might be more specifically part of the MAPK cascade

Conclusion

Overall, this is a well-constructed GO-CAM model that accurately represents the ERBB2-ERBB3 signaling pathway involved in myelination. It follows GO-CAM best practices and uses appropriate evidence codes and references. The model shows a clear flow of signal transduction from ligand binding to downstream kinase activation.

The model is scientifically accurate, has good evidence support, and effectively represents the biological pathway. Minor improvements could be made to connect the pathway more explicitly to the myelination process and to ensure all cellular location assertions have evidence.