Signaling Direction

[pwmellors]

I am under the impression that the direction of signaling (incoming versus outgoing) is dictated by which cell expresses the ligand, and which expresses the receptor. For example, if Cell A expresses ligand X, it will signal to Cell B expressing receptor Y (the opposite would not make sense to me biologically).

However, there are several instances in my data where the opposite is indeed true, where the receptor expressing cell is signaling to the ligand expressing cell. Case in point:

Here, CD226 (a known T-cell receptor), expressing T-cells are signaling TO Nectin-2 (a ligand) expressing endothelial cells.

Can someone clear this up? I have read through the manuscript, but still don't have a good sense of how directionality of signaling is determined.

[pwmellors]

I think the problem lies in how these are defined in the database, as CD226 is in fact defined as a ligand - I think this is probably not biologically correct. The same with CD96. These are both well described receptors.