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J. Biol. Chem., Vol. 276, Issue 45, 42213-42218, November 9, 2001
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From the The bone morphogenic proteins (BMPs) play a key
role in skeletal development and patterning. Using the technique of
differential display polymerase chain reaction (ddPCR), we have
identified a novel gene whose expression is increased during
BMP-2-induced differentiation of the prechondroblastic cell line,
MLB13MYC clone 17, to an osteoblastic phenotype. The
6.5-kilobase mRNA recognized by this ddPCR product is
increased 10-fold by BMP-2 treatment of the MLB13MYC clone 17 cells.
The mRNA recognized by this ddPCR product is also increased as
MC3T3-E1 cells recapitulate the program of osteoblast differentiation
during prolonged culture. The full-length transcript corresponding to
this ddPCR product was cloned from a MLB13MYC clone 17 cell cDNA
library. Analysis of the deduced amino acid sequence demonstrated that
this gene encodes a novel 126-kDa putative serine/threonine protein
kinase containing a nuclear localization signal. The kinase domain,
expressed in Escherichia coli, is capable of
autophosphorylation as well as phosphorylation of myelin basic protein.
The gene was, therefore, named BIKe
(BMP-2-Inducible Kinase). The BIKe nuclear localization signal
is able to direct green fluorescent protein to the nucleus in
transfected COS-7 cells. When stably expressed in MC3T3-E1 cells, BIKe
significantly decreases alkaline phosphatase activity and osteocalcin
mRNA levels and retards mineral deposition relative to vector
control. This novel kinase, therefore, is likely to play an
important regulatory role in attenuating the program of osteoblast differentiation.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AYe50249.
Cloning and Characterization of a Novel Protein Kinase That
Impairs Osteoblast Differentiation in Vitro*
§,, and
Division of Endocrinology, Diabetes,
Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota 55905 and
¶ Endocrine Unit, Massachusetts General Hospital, Harvard Medical
School, Boston, Massachusetts 02114
*
This work was supported by National Institutes of Health
Grant DK-36597 (to M. B. D.), National Institutes of Health and the American Society of Bone and Mineral Research Grant AR-45011 (to A. E. K.), and the Mayo Foundation (to A. E. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be sent: Endocrine Unit,
Massachusetts General Hospital, Harvard Medical School, Wellman 503, 50 Blossom St. Tel.: 617-726-3966; Fax: 617-726-7543; E-mail: demay@helix.mgh.harvard.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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