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Now I'll look at the Shc1/Grb2/Sos complex documentation in GO-CAM to understand best practices regarding this specific complex.

Now that I have reviewed the model and relevant information, I'll provide a review of GO-CAM model gomodel:62b4ffe300006474 (B cell receptor signaling pathway 1 in Mouse).

Review of GO-CAM Model 62b4ffe300006474: B cell receptor signaling pathway 1 (Mouse)

Overview

This model represents the B cell receptor (BCR) signaling pathway in mouse, focusing on the molecular interactions involving Shc1, Grb2, Sos1/2, and Syk proteins. The model describes a key signaling cascade that connects BCR activation to the Ras pathway.

Model Structure Assessment

The model contains 7 activities: 1. Sos1 - guanyl-nucleotide exchange factor activity (GO:0005085) 2. Grb2 - guanyl-nucleotide exchange factor adaptor activity (GO:0005091) 3. PR:P98083-2 (Shc1/p52Shc) - protein-macromolecule adaptor activity (GO:0030674) 4. Syk - protein tyrosine kinase activity (GO:0004713) 5. Cd79a - transmembrane signaling receptor activity (GO:0004888) 6. Cd79b - transmembrane signaling receptor activity (GO:0004888) 7. Sos2 - guanyl-nucleotide exchange factor activity (GO:0005085)

All activities are part of the B cell receptor signaling pathway (GO:0050853), which is appropriate.

Causal Relationships

The model includes these causal relationships: - Syk → Shc1 (RO:0002629, directly positively regulates) - Shc1 → Grb2 (RO:0002629, directly positively regulates) - Grb2 → Sos1 (RO:0002629, directly positively regulates) - Grb2 → Sos2 (RO:0002629, directly positively regulates)

These relationships accurately depict the directional flow of signaling in the BCR pathway based on the literature, where Syk phosphorylates Shc1, which recruits Grb2, which in turn recruits Sos1/2.

Evidence Assessment

The model includes good evidence support: - Syk's role is supported by experimental evidence (ECO:0000314, direct assay evidence) from PMID:9199344 - Shc1's role is supported by the same direct assay evidence - Grb2's role is also supported by direct assay evidence from PMID:9199344 - Sos1's role is supported by sequence orthology evidence (ECO:0000266) from PMID:11333268 and mutant phenotype evidence (ECO:0000315) from PMID:29844066 - Sos2's role lacks specific evidence annotation - The CD79a/b roles are supported by direct assay evidence from PMID:8626447

Strengths

  1. Accurate molecular pathway representation: The model correctly captures the key steps in the B cell receptor signaling pathway, showing how signals from the BCR are transmitted to activate the Ras pathway.

  2. Appropriate evidence: Most activities are backed by experimental evidence from relevant publications.

  3. Correct protein roles: The model accurately represents the roles of each protein, particularly the adaptor functions of Shc1 and Grb2, and the catalytic activity of Sos1/2.

  4. Use of protein isoforms: The model specifically uses the p52Shc isoform of Shc1 (PR:P98083-2), which is known to be important in this signaling context according to PMID:9199344.

Issues and Suggestions for Improvement

  1. Sos2 evidence: The Sos2 activity lacks specific evidence annotation. Based on the PMID:29844066 paper, there's evidence for functional redundancy between Sos1 and Sos2, which should be added as evidence.

  2. Missing CD79a/b connection: While CD79a and CD79b are included in the model, they lack causal connections to Syk. Based on literature, CD79a/b are phosphorylated after BCR cross-linking, creating docking sites for Syk. This causal relationship should be added.

  3. Missing BCR complex: The model doesn't explicitly show how the BCR itself connects to CD79a/b. Including a representation of the BCR complex would make the initiation of signaling clearer.

  4. Complex representation: According to the GO-CAM complex annotation guidelines, when the subunit carrying the molecular activity is known (as in this case), each protein should be represented separately with their specific activity. This is done correctly here. However, it might be useful to note that Shc1-Grb2-Sos forms a multiprotein complex, perhaps as a comment.

  5. Ras activation: The model doesn't show the ultimate target of Sos1/2, which is Ras activation. Adding this downstream event would complete the signaling cascade.

Biological Consistency

The model is consistent with the known biology of BCR signaling:

  1. As shown in PMID:9199344, BCR stimulation leads to Syk-dependent phosphorylation of Shc1, creating binding sites for Grb2, which then recruits Sos1/2 to activate Ras.

  2. The model correctly represents the role of p52Shc (PR:P98083-2) which contains the two phosphorylation sites (Y239 and Y313) that serve as binding sites for Grb2 according to the literature.

  3. The inclusion of both Sos1 and Sos2 reflects their functional redundancy in mouse, as demonstrated in the PMID:29844066 paper.

Conclusion

This GO-CAM model (gomodel:62b4ffe300006474) accurately represents a critical signaling pathway in B cell receptor activation. It correctly depicts the roles of key proteins and their causal relationships, with appropriate evidence support. The model could be enhanced by adding the missing causal connections for CD79a/b to Syk and by showing the downstream activation of Ras. Overall, the model is biologically sound and follows GO-CAM annotation best practices.