ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors.
A disintegrin and metalloprotease (ADAM) is a membrane-anchored metalloprotease implicated in the ectodomain shedding of cell surface proteins, including the ligands for epidermal growth factor (EGF) receptors (EGFR)/ErbB. It has been well documented that the transactivation of the EGFR plays critical roles for many cellular functions, such as proliferation and migration mediated through multiple G protein-coupled receptors (GPCRs). Recent accumulating evidence has suggested that ADAMs are the key metalloproteases activated by several GPCR agonists to produce a mature EGFR ligand leading to the EGFR transactivation. In this review, we describe the current knowledge on ADAMs implicated in mediating EGFR transactivation. The major focus of the review will be on the possible upstream mechanisms of ADAM activation by GPCRs as well as downstream signal transduction and the pathophysiological significances of ADAM-dependent EGFR transactivation.
Ohtsu
Haruhiko
H
Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, 3420 N. Broad St., Philadelphia, PA 19140, USA.
Dempsey
Peter J
PJ
Eguchi
Satoru
S
D051722:ADAM Proteins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
D043562:Receptors, G-Protein-Coupled; D066246:ErbB Receptors; D051722:ADAM Proteins