SB203580 Induces Prolonged B-Raf Activation and Promotes Neuronal Differentiation upon EGF Treatment of PC12 Cells

Seunghee Yoon^1,3, Rony Seger², Eui-Ju Choi³, and Young Sook Yoo^1*

¹Bioanalysis and Biotransformation Research Center, Korean Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650, Republic of Korea; fax: 82-2-958-5170; E-mail: ysyoo@kist.re.kr

²Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel; fax: 972-8-9344116; E-mail: rony.seger@weizmann.ac.il

³Graduate School of Biotechnology, Korea University, Seoul 136-701, Republic of Korea; E-mail: ejchoi@korea.ac.kr

^* To whom correspondence should be addressed.

Received December 24, 2003; Revision received February 4, 2004

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SB203580 is a p38 MAPK inhibitor that has been implicated in the activation of c-Raf. This study shows that the addition of SB203580 to PC12 cells causes the sustained activation of B-Raf but not of ERK. The addition of SB203580 prolonged the transient activation of both B-Raf and ERK by EGF alone. No significant change was detected in MAPKAPK-2 activity at low concentrations of SB203580, which induced neurite outgrowth in the EGF-stimulated PC12 cells. Therefore, these results indicate that SB203580 influences not only c-Raf as previously reported, but can also induce the activation of B-Raf, which in conjunction with EGF causes the sustained activation of ERK and differentiation in PC12 cells.

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KEY WORDS: B-Raf, SB203580, ERK, neurite outgrowth, nuclear translocation, PC12 cells

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