The role of protease activity in ErbB biology.
Proteases are now recognized as having an active role in a variety of processes aside from their recognized metabolic role in protein degradation. Within the ErbB system of ligands and receptors, proteases are known to be necessary for the generation of soluble ligands from transmembrane precursors and for the processing of the ErbB4 receptor, such that its intracellular domain is translocated to the nucleus. There are two protease activities involved in the events: proteases that cleave within the ectodomain of ligand (or receptor) and proteases that cleave the substrate within the transmembrane domain. The former are the ADAM proteases and the latter are the gamma-secretase complex and the rhomboid proteases. This review discusses the roles of each of these protease systems within the ErbB system.
Blobel
Carl P
CP
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Department of Medicine, Weil Medical College of Cornell University, New York, NY 10021, USA. blobelc@hss.edu
Carpenter
Graham
G
Freeman
Matthew
M
D051722:ADAM Proteins / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000378:metabolism*; D021381:Protein Transport; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
D051722:ADAM Proteins; D053829:Amyloid Precursor Protein Secretases; D008565:Membrane Proteins; D010447:Peptide Hydrolases; D018719:Erb-b2 Receptor Tyrosine Kinases