The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis.
A complex of RON(M1254T) with AMP-PNP and Mg(2+) reveals a substratelike positioning of Tyr1238 as well as likely catalysis-competent placement of the AMP-PNP and Mg(2+) components and indicates a tendency for cis phosphorylation. The structure shows how the oncogenic mutation may cause the constitutive activation and suggests a mechanistic hypothesis for the autophosphorylation of receptor tyrosine kinases.
Wang
Jing
J
OSI Pharmaceuticals, Inc., 1 Bioscience Park Drive, Farmingdale, New York 11735, USA. jwang@osip.com
Steinbacher
Stefan
S
Augustin
Martin
M
Schreiner
Patrick
P
Epstein
David
D
Mulvihill
Mark J
MJ
Crew
Andrew P
AP
D000266:Adenylyl Imidodiphosphate; D010766:Phosphorylation; D010770:Phosphotransferases; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D000266:Adenylyl Imidodiphosphate; D010770:Phosphotransferases; D020794:Receptor Protein-Tyrosine Kinases