The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling.
Item Type:Journal Article
Citation:Perkinton, MS, Standen, CL, Lau, KF, Kesavapany, S, Byers, HL, Ward, M, McLoughlin, DM, Miller, CC, `The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling? in The Journal of Biological Chemistry, 279, (21), 2004, pp 22084 - 22091
The c-Abl Tyrosine.pdf (published (publisher copy) peer-reviewed) 400.7Kb
The amyloid precursor protein (APP) is proteolytically processed to release a C-terminal domain that signals to the nucleus to regulate transcription of responsive genes. The APP C terminus binds to a number of phosphotyrosine binding (PTB) domain proteins and one of these, Fe65, stimulates APP nuclear signaling. Fe65 is an adaptor protein that contains a number of protein-protein interaction domains. These include two PTB domains, the second of which binds APP, and a WW domain that binds proline-rich ligands. One ligand for the Fe65WW domain is the tyrosine kinase c-Abl. Here, we show that active c-Abl stimulates APP/Fe65-mediated gene transcription and that this effect is mediated by phosphorylation of Fe65 on tyrosine 547 within its second PTB domain. The homologous tyrosine within the motif Tyr-(Leu/Met)-Gly is conserved in a variety of PTB domains, and this suggests that PTB tyrosine phosphorylation occurs in other proteins. As such, PTB domain phosphorylation may represent a novel mechanism for regulating the function of this class of protein.
European Union (EU)
Author: MCLOUGHLIN, DECLAN
Publisher:American Society for Biochemistry and Molecular Biology
Type of material:Journal Article
Series/Report no:The Journal of Biological Chemistry
Availability:Full text available