Effect of SB 203580 on the activity of c-Raf in vitro and in vivo
Authors: P Cohen
C A Hall-Jackson
M Goedert
P Hedge
Journal: Oncogene (1999)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: SAPK2a/p38; SB 203580; c-Raf; protein kinases; MAP kinase cascade
Affiliations: Department of Biochemistry, University of Dundee, Scotland.

Abstract:  The inhibition of SAPK2a/p38 (a mitogen activated protein (MAP) kinase family member) by SB 203580 depends on the presence of threonine at residue 106. Nearly all other protein kinases are insensitive to this drug because a more bulky residue occupies this site (Eyers et al., 1998). Raf is one of the few protein kinases that possesses threonine at this position, and we show that SB 203580 inhibits c-Raf with an IC50 of 2 microM in vitro. However, SB 203580 does not suppress either growth factor or phorbol ester-induced activation of the classical MAP kinase cascade in mammalian cells. One of the reasons for this is that SB 203580 also triggers a remarkable activation of c-Raf in vivo (when measured in the absence of the drug). The SB 203580-induced activation of c-Raf occurs without any increase in the GTP-loading of Ras, is not prevented by inhibitors of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase, and is not triggered by the binding of this drug to SAPK2a/p38. The paradoxical activation of c-Raf by SB 203580 (and by another structurally unrelated c-Raf inhibitor) suggests that inhibitors of the kinase activity of c-Raf may not be effective as anti-cancer drugs. 

Retracted: No

PubPeer comments:
 Figure 1Euff1aduplication of data ![file] , 
 Dear PubPeer, Thank you for notifying me this mistake of duplication of Fig. 1E in our publication: Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning The Journal of Experimental Medicine (2018) - 1 Comment pubmed: 29305395 doi: 10.1084 jem.20171012 issn: 0022-1007 issn: 1540-9538 Takahiro Seki , Kayoko Hosaka , Carina Fischer , Sharon Lim , Patrik Andersson , Mitsuhiko Abe , Hideki Iwamoto , Yanyan Gao , Xinsheng Wang , Guo-Hua Fong , Yihai Cao author has email. We apologize for this mistake and inconvenience. I have contacted the first author Dr. Takahiro Seki who had done these experiments and figure editing. Dr. Seki has responded to this this alert issue. Dr. Seki has gone through his original data and carefully analyzed this mistake. It appears that he made a mistake during assembling this figure. The duplicated image belongs to the Anti-R1 and Anti-R2 combination group, which was also mistakenly used in the anti-R2 alone group. He explains that during assembling of this figure, many image windows were open simultaneously and the labelings were similar. Therefore, he mistakenly cut this same picture twice. Please read his response letter in the attached text. We sincerely apologize for this mistake. We have no intention to do any untruthful scientific research. This mistake was created without our own notice. We are very grateful that you have spotted this mistake for us. We will contact the JEM journal to make a correction as soon as possible. Thanks so much. Best wishes, Yihai Cao The first author Dr. Takahiro Sekiu00b4s response: Dear PubPeer, I am the first author of the paper, entitled Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning. I was fully responsible for the project including doing the experiment and editing the figure for the manuscript. Thank you very much for pointing this mistake. I am deeply sorry to misuse the images. We sincerely apologize to make this mistake happened. What you pointed out the images is very sadly correct, those are the same images from a picture of subcutaneous white adipose tissue treated with the Anti-VEGFR1 antibody combined with Anti-VEGFR2 antibody. The wrong image is the group of Anti-VEGFR2, not the combination group. The two images were created for the group of the combination. During the assembling of the figure, a lot of the windows would open and the file name was similar as Anti-VEGFR2 group, therefore, mistakenly was accidentally placed on the Anti-VEGFR2 alone. We go through all images in this paper and there is nothing to use duplications. This mistake never affects our findings and conclusions. We are sincerely not doing wrong and do never intentionally put those images on the figure. We will notice the mistake of JEM for an erratum by replacing the correct figure. We are again sincerely sorry to cause this inconvenience and understanding the situation. Yours sincerely, Takahiro Seki , 
 From the author s correction in the journal, the new version of fig1A looks strange. It seems that the order of the CD31 image panels got scrambled. , 
 #3 Dear Dr Fischeri, Thank you for your excellent comment. I completely agree. This must be a mistake during correction by the journal production department. We will contact them immediately. The NIIgG and R1 should have switched the position of D31 pictures in Fig. 1A. Thanks for finding this mistake. Sincerely Yihai Cao ,