A protein methyl transferase, PRMT5, selectively blocks oncogenic ras-p21 mitogenic signal transduction

Lyndon Chie, Jeffry R. Cook, Denise Chung, Ralf Hoffmann, Zhihong Yang, Youngsun Kim, Sidney Pestka, Matthew R. Pincus

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


A Janus-2 (JAK-2) binding protein, JBP1, has been found to function as an arginine methyl transferase and is now designated PRMT5. Co-injection of plasmids encoding this protein together with oncogenic (Val 12-containing) ras-p21 protein into Xenopus laevis oocytes results in strong inhibition of oncogenic p21-induced oocyte maturation. This inhibition appears to be dependent on the methyl transferase function since a partially active R368A mutant shows diminished ability to inhibit Val 12-p21-induced oocyte maturation, and an almost totally inactive GAGRG (365-369) deletion mutant fails to inhibit Val 12-p21-induced maturation. In contrast, PRMT5 (JBP1) does not inhibit insulin-induced oocyte maturation. Since insulin-induced maturation depends on activation of cellular ras-p21, PRMT5 does not appear to inhibit the wild-type p21 protein. We also find that arginine methyl transferase inhibitors strongly block oncogenic ras-p21-activated, but not insulin-activated, wild-type ras-p21-induced oocyte maturation. Thus signaling by oncogenic p21 appears to involve methyltransferases uniquely. Surprisingly, the active site peptide, Gly-Arg-Gly, strongly suppresses insulin-induced maturation but has no effect on Val 12-p21-induced maturation. This peptide may therefore be useful in defining steps in the wild-type ras pathway.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalAnnals of Clinical and Laboratory Science
Issue number2
StatePublished - Mar 2003
Externally publishedYes


  • Insulin
  • JAK-2-binding protein
  • Oncogenic ras-p21
  • Protein arginine methyltrasferase (PRMT5)


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