An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors.
Recent crystallographic studies have provided significant new insight into how receptor tyrosine kinases from the EGF receptor or ErbB family are regulated by their growth factor ligands. EGF receptor dimerization is mediated by a unique dimerization arm, which becomes exposed only after a dramatic domain rearrangement is promoted by growth factor binding. ErbB2, a family member that has no ligand, has its dimerization arm constitutively exposed, and this explains several of its unique properties. We outline a mechanistic view of ErbB receptor homo- and heterodimerization, which suggests new approaches for interfering with these processes when they are implicated in human cancers.
Burgess
Antony W
AW
Cooperative Research Centre for Cellular Growth Factors, P.O. Box 2008, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Cho
Hyun-Soo
HS
Eigenbrot
Charles
C
Ferguson
Kathryn M
KM
Garrett
Thomas P J
TP
Leahy
Daniel J
DJ
Lemmon
Mark A
MA
Sliwkowski
Mark X
MX
Ward
Colin W
CW
Yokoyama
Shigeyuki
S
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018739:Oncogene Proteins v-erbB / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D006133:Growth Substances; D008024:Ligands; D018739:Oncogene Proteins v-erbB; D066246:ErbB Receptors