Phosphatase and feedback regulation of Raf-1 signaling.
The Raf-1 kinase is an effector of Ras GTPases that lies at the apex of the three-tier Raf/MEK/ERK pathway. Raf-1 activation is a complex process that entails two major events--relief of autoinhibition imposed by the regulatory domain and kinase domain activation. Recent studies indicate that the transition of Raf-1 from an active to an inactive state bears similar complexity to the activation process. Both these events require dynamic changes in Raf-1 phosphorylation. Here, we discuss the critical role of phosphatases and feedback phosphorylation during activation and inactivation of Raf-1 signaling.
Dhillon
Amardeep S
AS
Signaling and Proteomics Group, Beatson Institute for Cancer Research, Glasgow, UK. A.Dhillon@beatson.gla.ac.uk
von Kriegsheim
Alex
A
Grindlay
Joan
J
Kolch
Walter
W
D000818:Animals; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D019908:Proto-Oncogene Proteins c-raf; D010744:Phosphoric Monoester Hydrolases