The ErbB Signaling Network

Extending the Variation of Signaling Complexes by Diversification of Ligand Recognition 

According to the model implying bivalence of ErbB binding ligands, each EGF-like domain can select its own unique set of preferred receptor dimers, 

---

Alroy, I., and Y. Yarden. The ErbB signaling network in embryogenesis and oncogenesis signal diversification through combinatorial ligand-receptor interactions. FEBS-Lett. 410 83-86.1997. 

Yarden, Y., and M. X. Sliwkowski. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2 127-37.2001. 

A protein microarray study by Jones et al. (33) was designed to test the affinity of all proteins that contain SH2 and PTB domains, which specify binding to the phosphorylated domains of all four ErbB family members. The study uncovered that some ErbB family members were more promiscuous than others, which has important implications for the ErbB signaling network in general and specifically in that the promiscuous ErbB family members are much more commonly overexpressed in several cancer cell types. Eurthermore, 116 new ErbB interaction partners were discovered. Another study by Schulze et al. (34) was also designed to identify all interaction partners for the phosphorylated ErbB family members but using a novel methodology that combines SILAC and LC-MS/MS. This study defined the specific ErbB sites where the interaction partners bind. 

---