MEK inhibition and phosphorylation of serine 4 on B23 are two coincident events in mitosis

被引:11
作者
Hayne, C [1 ]
Xiang, XQ [1 ]
Luo, ZJ [1 ]
机构
[1] Boston Univ, Sch Med, Dept Med, Sect Endocrinol,Diabet Res Unit, Boston, MA 02118 USA
关键词
Raf; MEK; ERK; cell cycle; mitosis; B23/numatrin/nucleophosmin; PLK1; CDK;
D O I
10.1016/j.bbrc.2004.07.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have shown that activation of the Raf/MEK/ERK pathway is necessary for G2/M transition. However, as for the activation state of MEK in mitosis the conclusion is not consistent. Here we show that MEK is inhibited in mitosis. In addition, we identify a multifunctional protein named B23 that strongly cross-reacts with a phospho-MEK antibody in mitotic cells. Sequence homology between the N-terminus surrounding Ser 4 of B23 and the Raf phosphorylation site on MEK suggests a mechanism for cross-reaction of the antibody. Thus, mutation of Ser 4 to alanine abolishes cross-reactivity between B23 and the phospho-MEK antibody. Our findings may explain the discrepancy of results obtained with the use of phospho-MEK antibody regarding the activation state of MEK in mitosis. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:675 / 680
页数:6
相关论文
共 23 条
[1]   RAS GENES [J].
BARBACID, M .
ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :779-827
[2]   Phosphorylation regulates nucleophosmin targeting to the centrosome during mitosis as detected by cross-reactive phosphorylation-specific MKK1/MKK2 antibodies [J].
Cha, H ;
Hancock, C ;
Dangi, S ;
Maiguel, D ;
Carrier, F ;
Shapiro, P .
BIOCHEMICAL JOURNAL, 2004, 378 :857-865
[3]   RAF1-activated MEK1 is found on the Golgi apparatus in late prophase and is required for Golgi complex fragmentation in mitosis [J].
Colanzi, A ;
Sutterlin, C ;
Malhotra, V .
JOURNAL OF CELL BIOLOGY, 2003, 161 (01) :27-32
[4]   Mechanism of mitosis-specific activation of MEK1 [J].
Harding, A ;
Giles, N ;
Burgess, A ;
Hancock, JF ;
Gabrielli, BG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) :16747-16754
[5]   Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by nocodazole [J].
Hayne, C ;
Tzivion, G ;
Luo, ZJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (41) :31876-31882
[6]   Different kinases phosphorylate nucleophosmin/B23 at different sites during G2 and M phases of the cell cycle [J].
Jiang, PS ;
Chang, JH ;
Yung, BYM .
CANCER LETTERS, 2000, 153 (1-2) :151-160
[7]   Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions [J].
Kolch, W .
BIOCHEMICAL JOURNAL, 2000, 351 :289-305
[8]   Characterization of Raf-1 activation in mitosis [J].
Laird, AD ;
Morrison, DK ;
Shalloway, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (07) :4430-4439
[9]   Oncoprotein signalling and mitosis [J].
Laird, AD ;
Shalloway, D .
CELLULAR SIGNALLING, 1997, 9 (3-4) :249-255
[10]   The MAP kinase pathway is required for entry into mitosis and cell survival [J].
Liu, X ;
Yan, S ;
Zhou, TH ;
Terada, Y ;
Erikson, RL .
ONCOGENE, 2004, 23 (03) :763-776