Skip to content

Now I'll review the GO-CAM model with ID 6197061700001622 based on the information gathered.

Review of GO-CAM Model: gomodel:6197061700001622

Model Overview

This GO-CAM model (gomodel:6197061700001622) is titled "Epidermal growth factor receptor signaling pathway 2 (Mouse)" and represents molecular activities and causal relationships in the EGFR signaling pathway in mouse (NCBITaxon:10090).

Model Structure and Components

The model contains four main molecular activities:

  1. Activity 1 (gomodel:6197061700001622/6197061700001985):
  2. Enabled by: Adam17 (MGI:MGI:1096335)
  3. Molecular function: Metallodipeptidase activity (GO:0070573)
  4. Occurs in: Plasma membrane (GO:0005886)
  5. Part of: Signaling receptor ligand precursor processing (GO:0140448)

  6. Causally upstream of (positive effect) Activity 4

  7. Activity 2 (gomodel:6197061700001622/6197061700001628):

  8. Enabled by: Egfr (MGI:MGI:95294)
  9. Molecular function: Transmembrane receptor protein tyrosine kinase activity (GO:0004714)
  10. Occurs in: Plasma membrane (GO:0005886)

  11. Part of: Epidermal growth factor receptor signaling pathway (GO:0007173)

  12. Activity 3 (gomodel:6197061700001622/6197061700001769):

  13. Enabled by: Mep1a (MGI:MGI:96963)
  14. Molecular function: Metallodipeptidase activity (GO:0070573)
  15. Occurs in: Plasma membrane (GO:0005886)
  16. Part of: Signaling receptor ligand precursor processing (GO:0140448)

  17. Causally upstream of (positive effect) Activity 4

  18. Activity 4 (gomodel:6197061700001622/6197061700001624):

  19. Enabled by: Tgfa (MGI:MGI:98724)
  20. Molecular function: Receptor ligand activity (GO:0048018)
  21. Occurs in: Extracellular space (GO:0005615)
  22. Part of: Epidermal growth factor receptor signaling pathway (GO:0007173)
  23. Directly positively regulates Activity 2

Evidence Support

The model is supported by evidence from several publications: - PMID:14993236: Mutant phenotype evidence for ADAM17's role in processing EGFR ligands - PMID:7752576: Direct assay evidence for EGFR and its activation by TGFα - PMID:22923609: Sequence orthology evidence for MEP1A's role in processing EGFR ligands

Biological Content Assessment

The model accurately represents the EGFR signaling pathway in mouse, focusing on:

  1. Ligand processing: Both ADAM17 (Activity 1) and MEP1A (Activity 3) are shown to process TGFα (Activity 4), which is consistent with the literature. ADAM17 is a well-established sheddase for TGFα as evidenced in PMID:14993236, and MEP1A has been shown to process TGFα as supported by PMID:22923609.

  2. Receptor activation: TGFα (Activity 4) directly positively regulates EGFR (Activity 2), which is consistent with the receptor-ligand relationship.

  3. Causal chain: The model correctly depicts the causal flow from sheddase activity (ADAM17, MEP1A) → ligand processing (TGFα) → receptor activation (EGFR).

Assessment Against GO-CAM Best Practices

The model adheres to GO-CAM best practices in the following ways:

  1. Proper causality representation: The model uses appropriate causal relationships with correct directionality:
  2. RO:0002304 (causally upstream of, positive effect) for sheddase → ligand relationship

  3. RO:0002629 (directly positively regulates) for ligand → receptor relationship

  4. Cellular locations: All activities are appropriately annotated with cellular locations that are biologically accurate (plasma membrane for sheddases and receptor, extracellular space for the ligand).

  5. Process annotations: Each activity is correctly annotated with the biological process it is a part of.

  6. Evidence support: The model includes appropriate evidence codes and PMIDs for each assertion.

Areas for Improvement

The model is biologically accurate and complies with GO-CAM best practices, but a few minor improvements could be considered:

  1. Downstream signaling: The model could be expanded to include downstream signaling events after EGFR activation, such as MAPK pathway activation, which is mentioned in PMID:22923609.

  2. Additional ligands: While the model focuses on TGFα, EGFR signaling also involves other ligands processed by ADAM17, such as amphiregulin, HB-EGF, and epiregulin (as described in PMID:14993236). The model could be expanded to include these, if the goal is a more comprehensive representation of EGFR signaling.

  3. Feedback regulation: The model could include feedback regulatory mechanisms known to modulate EGFR signaling.

Conclusion

The GO-CAM model 6197061700001622 provides an accurate and well-structured representation of the EGFR signaling pathway in mouse, focusing on the processing of TGFα by ADAM17 and MEP1A, and the subsequent activation of the EGFR. The model adheres to GO-CAM best practices in terms of causal relationships, cellular locations, and evidence support. The biological content is consistent with the scientific literature and represents our current understanding of EGFR signaling.