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Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx.

Publication ,  Journal Article
Walsh, S; Margolis, SS; Kornbluth, S
Published in: Molecular cancer research : MCR
February 2003

The cyclin B1/Cdc2 complex regulates many of the dramatic cellular rearrangements observed at mitosis. Although predominantly cytoplasmic during interphase, this kinase complex translocates precipitously to the nucleus at the G(2)-M transition. The interphase cytoplasmic location of cyclin B1/Cdc2 reflects continuous, albeit slow, nuclear import and much more rapid nuclear export. In contrast, the sudden nuclear accumulation of the complex before entry into mitosis reflects a marked increase in the import rate, with a concomitant inhibition of cyclin B1 nuclear export. These dynamic changes in cyclin B1/Cdc2 localization are regulated by phosphorylation of four serines within a region of cyclin B1 known as the cytoplasmic retention sequence (CRS). Phosphorylation of all four serines is required for rapid nuclear entry, whereas phosphorylation of only the last in the series (Ser 113) is required to prevent nuclear export by CRM1. As these residues represent key loci of regulation, it is important to identify the kinases acting on these sites. Here we report that Xenopus cyclin B1 is regulated by both Erk and Plx kinases, and that Cdc2, counter to previous speculation, is not required for CRS phosphorylation. Phosphorylation of the first two of the CRS serines (Ser 94 and Ser 96) is catalyzed by Erk in the Xenopus system. Although it was previously reported that Ser 113 is a Plx substrate, we were unable to observe phosphorylation of this residue in isolation by purified Plx. Rather, in contrast to previously published data, we have found that the penultimate CRS serine (Ser 101) is a Plx substrate. Collectively, these data demonstrate a new role for Erk in mitotic regulation, identify the Ser 101-directed kinase, and provide a picture of cyclin B1/Cdc2 regulation by the combinatorial action of distinct kinases.

Duke Scholars

Published In

Molecular cancer research : MCR

EISSN

1557-3125

ISSN

1541-7786

Publication Date

February 2003

Volume

1

Issue

4

Start / End Page

280 / 289

Related Subject Headings

  • Xenopus laevis
  • Xenopus Proteins
  • Serine
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Oocytes
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Walsh, S., Margolis, S. S., & Kornbluth, S. (2003). Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx. Molecular Cancer Research : MCR, 1(4), 280–289.
Walsh, Susan, Seth S. Margolis, and Sally Kornbluth. “Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx.Molecular Cancer Research : MCR 1, no. 4 (February 2003): 280–89.
Walsh S, Margolis SS, Kornbluth S. Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx. Molecular cancer research : MCR. 2003 Feb;1(4):280–9.
Walsh, Susan, et al. “Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx.Molecular Cancer Research : MCR, vol. 1, no. 4, Feb. 2003, pp. 280–89.
Walsh S, Margolis SS, Kornbluth S. Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and Plx. Molecular cancer research : MCR. 2003 Feb;1(4):280–289.

Published In

Molecular cancer research : MCR

EISSN

1557-3125

ISSN

1541-7786

Publication Date

February 2003

Volume

1

Issue

4

Start / End Page

280 / 289

Related Subject Headings

  • Xenopus laevis
  • Xenopus Proteins
  • Serine
  • Protein Serine-Threonine Kinases
  • Phosphorylation
  • Oocytes
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System