Protein Arginine Methyltransferase 5 Regulates ERK1/2 Signal Transduction Amplitude and Cell Fate Through CRAF

Pedro Andreu-Pérez, Rosaura Esteve-Puig, Carlos de Torre-Minguela, Marta López-Fauqued, Joan Josep Bech-Serra, Stephan Tenbaum, Elena R. García-Trevijano, Francesc Canals, Glenn Merlino, Matías A. Ávila, Juan A. Recio*

*To whom correspondence should be addressed. E-mail: juan.recio{at}vhir.org

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• Fig. S1. MTA increases ERK1/2 phosphorylation in response to HGF in primary rat hepatocytes.
• Fig. S2. Modulation of HGF induced MEK1/2-ERK1/2 signaling by MTA in melanoma cells.
• Fig. S3. MTA modulates ERK1/2 phosphorylation upon specific growth factor treatment in human cells, and protein methylation inhibition modulates ERK1/2 signal amplitude in response to HGF.
• Fig. S4. PRMT1, PRMT3, and PRMT8 are not responsible for the MTA-mediated effect.
• Fig. S5. MTA signal amplitude modulation of ERK1/2 is RAS activation–dependent.
• Fig. S6. CRAF and BRAF immunoprecipitate and colocalize with PRMT5 in the cytoplasm.
• Fig. S7. MTA regulates growth factor–induced BRAF kinase activity.
• Fig. S8. Differential activation of RAF isoforms by growth factors.
• Fig. S9. MTA treatment inhibits CRAF degradation in SKMel147 cells.
• Fig. S10. BRAF^R671K mutant shows the same response as CRAF^R563K. ARAF stability is not regulated by MTA in SKMel147 cells.
• Fig. S11. A small fraction of total CRAF is recruited to the membrane in response to growth factor signaling. Detection by MALDI of both the unmethylated and the methylated CRAF peptides.
• Fig. S12. BRAF is in vivo methylated. BRAF^R671K mutant mimics the MTA-induced effects on PC12 cells.
• Fig. S13. PC12 differentiation assay.
• Methods
• References

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© 2011 American Association for the Advancement of Science