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Molecular and Cellular Biology, July 2006, p. 5300-5309, Vol. 26, No. 14
0270-7306/06/$08.00+0     doi:10.1128/MCB.00273-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mechanistic Studies of the Mitotic Activation of Mos

Jianbo Yue* and James E. Ferrell Jr

Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-5174

Received 13 February 2006/ Returned for modification 15 March 2006/ Accepted 3 May 2006

The protein kinase Mos is responsible for the activation of MEK1 and p42 mitogen-activated protein kinase during Xenopus oocyte maturation and during mitosis in Xenopus egg extracts. Here we show that the activation of Mos depends upon the phosphorylation of Ser 3, a residue previously implicated in the regulation of Mos stability; the dephosphorylation of Ser 105, a previously unidentified phosphorylation site conserved in Mos proteins; and the regulated dissociation of Mos from CK2ß. Mutation of Ser 3 to alanine and/or mutation of Ser 105 to glutamate produces a Mos protein that is defective for M-phase activation, as assessed by in vitro kinase assays, and defective for induction of oocyte maturation and maintenance of the spindle assembly checkpoint in extracts. Interestingly, Ser 105 is situated at the beginning of helix {alpha}C in the N-terminal lobe of the Mos kinase domain. Changes in the orientation of this helix have been previously implicated in the activation of Cdk2 and Src family tyrosine kinases. Our work suggests that Ser 105 dephosphorylation represents a novel mechanism for reorienting helix {alpha}C.


* Corresponding author. Mailing address: Stanford University School of Medicine, Department of Molecular Pharmacology, CCSR Room 3155, Stanford, CA 94305-5174. Phone: (650) 498-5117. Fax: (650) 723-2253. E-mail: jyue{at}Stanford.edu.


Molecular and Cellular Biology, July 2006, p. 5300-5309, Vol. 26, No. 14
0270-7306/06/$08.00+0     doi:10.1128/MCB.00273-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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