A novel role for Cdk1/cyclin B in regulating B-raf activation at mitosis.

Molecular Biology of the Cell
Sergiy I Borysov, T M Guadagno

Abstract

MAPK activity is important during mitosis for spindle assembly and maintenance of the spindle checkpoint arrest. We previously identified B-Raf as a critical activator of the MAPK cascade during mitosis in Xenopus egg extracts and showed that B-Raf activation is regulated in an M-phase-dependent manner. The mechanism that mediates B-Raf activation at mitosis has not been elucidated. Interestingly, activation of 95-kDa B-Raf at mitosis does not require phosphorylation of Thr-599 and Ser-602 residues (Thr-633 and Ser-636 in Xenopus B-Raf), previously shown to be essential for B-Raf activation by Ras. Instead, we provide evidence for Cdk1/cyclin B in mediating mitotic activation of B-Raf. In particular, Cdk1/cyclin B complexes associate with B-Raf at mitosis in Xenopus egg extracts and contribute to its phosphorylation. Mutagenesis and in vitro kinase assays demonstrated that Cdk1/cyclin B directly phosphorylates B-Raf at Serine-144, which is part of a conserved Cdk1 preferential consensus site (S(144)PQK). Importantly, phosphorylation of Ser-144 is absolutely required for mitotic activation of B-Raf and subsequent activation of the MAPK cascade. However, substitution of a phospho-mimicking amino acid at Ser-144 failed to produce ...Continue Reading

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Citations

Nov 15, 2011·Nature Medicine·Ainhoa MielgoDavid A Cheresh
May 5, 2011·Molecular Interventions·Paul DentSteven Grant
Nov 4, 2015·Journal of Cellular Biochemistry·Erika IwamotoYuji Nakayama
Jan 23, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuichiro KaiboriYuji Nakayama
Oct 16, 2015·Journal of Cell Science·Inbal WortzelRony Seger

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