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Now I'll formulate my review of the GO-CAM model.

GO-CAM Model Review: Activation of ALK and LTK by ALKAL1 and ALKAL2 cytokines (Human)

Model ID: gomodel:61e0e55600002253

Overview

The model represents the activation of two receptor tyrosine kinases, ALK (Anaplastic Lymphoma Kinase) and LTK (Leukocyte Tyrosine Kinase), by their ligands ALKAL1 (also known as FAM150A or AUG-beta) and ALKAL2 (also known as FAM150B or AUG-alpha). The model captures the cytokine-receptor interactions and the resulting signaling in the cell surface receptor protein tyrosine kinase signaling pathway.

Biological Content Assessment

This GO-CAM model accurately represents the current understanding of ALK and LTK receptor activation by ALKAL1 and ALKAL2 ligands, as supported by recent literature. The scientific content aligns well with the research described in the cited papers, particularly PMID:30061385, PMID:34646012, and PMID:34819673, which detail the structural basis and mechanisms of cytokine-mediated activation of these receptors.

Key biological aspects represented correctly: 1. ALKAL1 and ALKAL2 function as extracellular cytokines (GO:0005125) that occur in the extracellular space (GO:0005615) 2. ALK and LTK are transmembrane receptor tyrosine kinases (GO:0004714) located in the plasma membrane (GO:0005886) 3. Both receptors are involved in the cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169) 4. ALK also is shown to have heparin binding activity (GO:0008201), which is supported by the literature

Structure and Organization

The model appropriately uses the following causal associations: - "RO:0002629" (directly positively regulates) to show how the cytokines ALKAL1 and ALKAL2 activate their respective receptors - "RO:0002304" (causally upstream of, positive effect) to represent the activity of ALK's heparin binding domain in supporting receptor function

Technical Assessment

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

  1. For cytokines (ligands):
  2. ALKAL1 and ALKAL2 correctly enable cytokine activity (GO:0005125), which is a child of receptor ligand activity
  3. They occur in the extracellular space (GO:0005615) as expected
  4. They are properly shown as part of the cell surface receptor signaling pathway (GO:0007169)

  5. The causal relation "directly positively regulates" is correctly used to show how they activate their receptors

  6. For receptors:

  7. ALK and LTK correctly enable transmembrane receptor protein tyrosine kinase activity (GO:0004714)
  8. They are properly shown as occurring in the plasma membrane (GO:0005886)

  9. They are part of the appropriate signaling pathway (GO:0007169)

  10. Additional features:

  11. The model correctly represents ALK's heparin binding activity (GO:0008201), which according to recent literature helps regulate receptor activation

Strengths

  1. Comprehensive representation of both ALK and LTK signaling through their respective ligands
  2. Inclusion of ALK's heparin binding activity, which is an important regulatory feature
  3. Well-supported by multiple peer-reviewed publications
  4. Proper use of GO terms and relation types
  5. Correct cellular locations for all components

Possible Improvements

  1. Receptor Downstream Effects: The model could be expanded to show the downstream effectors of ALK and LTK activation, such as phosphorylation of adapter proteins and activation of MAPK or PI3K pathways, which are mentioned in the scientific literature.

  2. Receptor Dimerization: Recent structural studies (PMID:34819673) indicate that ALK and LTK dimerize upon ligand binding. This feature could be explicitly captured in the model.

  3. Ligand Specificity: The literature suggests that while ALKAL1 can activate both receptors, ALKAL2 is more specific for ALK. This differential activation potency could be represented.

  4. EGF-like Domain Role: The research indicates that the EGF-like domain of ALK is critical for ligand binding and receptor activation. This domain-specific information could be incorporated.

Conclusion

This GO-CAM model is scientifically accurate, well-structured, and follows the GO-CAM best practices for representing receptor-ligand interactions. It effectively captures the core biology of ALK and LTK activation by ALKAL1 and ALKAL2. The model is parsimonious while including key regulatory features like ALK's heparin binding activity. With some potential expansions to include downstream signaling effects, it could provide even greater utility to the scientific community.