Regulation of RKIP binding to the N-region of the Raf-1 kinase.
The Raf kinase inhibitory protein (RKIP) binds to Raf-1 interfering with binding of the MEK substrate and potentially also Raf-1 activation. In response to mitogen stimulation RKIP dissociates from Raf-1 and later re-associates. Here, using a combination of mutational approaches, biochemical studies, peptide arrays and plasmon surface resonance (BIAcore), we fine map and characterize a minimal 24 amino acid long RKIP binding domain in the Raf-1 N-region, which consists of constitutive elements at both flanks and a center element that is regulated by phosphorylation and enhances the re-binding of RKIP to Raf-1 in the later phase of mitogen stimulation.
Park
Sungdae
S
Medical University of Ohio, Department of Biochemistry and Cancer Biology, 3035 Arlington Avenue, Toledo, OH 43614-5804, USA.
Rath
Oliver
O
Beach
Sandy
S
Xiang
Xiaoqin
X
Kelly
Sharon M
SM
Luo
Zhijun
Z
Kolch
Walter
W
Yeung
Kam C
KC
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods
D008934:Mitogens; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D019908:Proto-Oncogene Proteins c-raf; D020930:MAP Kinase Kinase Kinases