Format

Send to

Choose Destination
Pharmacol Ther. 2009 Apr;122(1):1-8. doi: 10.1016/j.pharmthera.2008.11.008. Epub 2008 Dec 16.

Functional selectivity of EGF family peptide growth factors: implications for cancer.

Author information

1
Purdue University School of Pharmacy and Purdue Cancer Research Center, West Lafayette, IN 47907-2064, USA.

Abstract

Breast, prostate, pancreatic, colorectal, lung, and head and neck cancers exploit deregulated signaling by ErbB family receptors and their ligands, EGF family peptide growth factors. EGF family members that bind the same receptor are able to stimulate divergent biological responses both in cell culture and in vivo. This is analogous to the functional selectivity exhibited by ligands for G-protein coupled receptors. Here we review this literature and propose that this functional selectivity of EGF family members is due to distinctions in the conformation of the liganded receptor and subsequent differences in the sites of receptor tyrosine phosphorylation and receptor coupling to signaling effectors. We also discuss the roles of divergent ligand activity in establishing and maintaining malignant phenotypes. Finally, we discuss the potential of mutant EGF family ligands as cancer chemotherapeutics targeted to ErbB receptors.

PMID:
19135477
PMCID:
PMC2665203
DOI:
10.1016/j.pharmthera.2008.11.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center