Many receptor tyrosine kinases exist as families of related proteins; for example, there are four known mammalian ErbB-type receptors. Additional complexity comes from having many ligands that can bind to the family of receptors (more than 10 ligands have been identified for the ErbB family of receptors). Sweeney et al. expressed a single type of ErbB receptor in cells that completely lack ErbB receptors and showed that four different ligands for this receptor resulted in the phosphorylation of different tyrosine residues on the activated receptors and activated different signaling pathways. Their data suggest that a single receptor homodimer can discriminate among different ligands, providing a mechanism by which the signaling repertoire of a single receptor can be expanded and specified.
Sweeney, C., Lai, C., Riese, D.J. II, Diamonti, J., Cantley, L.C., and Carraway, K.L. III (2000) Ligand discrimination in signaling through an ErbB4 receptor homodimer. J. Biol. Chem. 275: 19803-19807. [Abstract] [Full Text]