RT Journal Article
T1 Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol
A1 Gutiérrez Uzquiza, Álvaro
A1 Colon-Gonzalez, Francheska
A1 Leonard, Thomas A.
A1 Canagarajah, Bertram J.
A1 Wang, HongBin
A1 Mayer, Bruce J.
A1 Hurley, James H.
A1 Kazanietz, Marcelo G.
AB Chimaerins, a family of GTPase activating proteins for the small G-protein Rac, have been implicated in development, neuritogenesis and cancer. These Rac-GTPase activating proteins are regulated by the lipid second messenger diacylglycerol generated by tyrosine kinases such as the epidermal growth factor receptor. Here we identify an atypical proline-rich motif in chimaerins that binds to the adaptor protein Nck1. Unlike most Nck1 partners, chimaerins bind to the third SH3 domain of Nck1. This association is mediated by electrostatic interactions of basic residues within the Pro-rich motif with acidic clusters in the SH3 domain. Epidermal growth factor promotes the binding of β2-chimaerin to Nck1 in the cell periphery in a diacylglycerol-dependent manner. Moreover, β2-chimaerin translocation to the plasma membrane and its peripheral association with Rac1 requires Nck1. Our studies underscore a coordinated mechanism for β2-chimaerin activation that involves lipid interactions via the C1 domain and protein-protein interactions via the N-terminal proline-rich region.
SN 2041-1723
YR 2013
FD 2013-05-14
LK https://hdl.handle.net/20.500.14352/93524
UL https://hdl.handle.net/20.500.14352/93524
LA eng
NO Gutierrez-Uzquiza A, Colon-Gonzalez F, Leonard TA, Canagarajah BJ, Wang H, Mayer BJ, et al. Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol. Nat Commun 2013;4:1849. https://doi.org/10.1038/ncomms28
NO National Institutes of Health
NO Organización Europea de Biología Molecular
DS Docta Complutense
RD 8 abr 2025