SB203580 induces prolonged B-Raf activation and promotes neuronal differentiation upon EGF treatment of PC12 cells.
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.
Bioanalysis and Biotransformation Research Center, Korean Institute of Science and Technology, Cheongryang, Seoul 130-650, Republic of Korea.
Seunghee
S
Yoon
Rony
R
Seger
Eui-Ju
EJ
Choi
Young Sook
YS
Yoo
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D000099190:MAP-Kinase-Activated Kinase 2
D004815:Epidermal Growth Factor; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D048493:Proto-Oncogene Proteins B-raf; D011725:Pyridines; D000099190:MAP-Kinase-Activated Kinase 2; C482123:Braf protein, rat; C093642:SB 203580