DOI: 10.1073/pnas.0503891102. Sequential phosphorylation of CCAAT enhancer-binding protein β by MAPK and glycogen synthase kinase 3β is required for adipogenesis

Sequential phosphorylation of CCAAT enhancer-binding protein β by MAPK and glycogen synthase kinase 3β is required for adipogenesis

10.1073/pnas.0503891102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

CCAAT enhancer-binding protein (C/EBP)β, C/EBPα, and peroxisome proliferator activated receptor (PPAR)γ act in a cascade where C/EBPβ activates expression of C/EBPα and PPARγ, which then function as pleiotropic activators of genes that produce the adipocyte phenotype. When growth-arrested 3T3-L1 preadipocytes are induced to differentiate, C/EBPβ is rapidly expressed but still lacks DNA-binding activity. After a long (14-hour) lag, glycogen synthase kinase 3β enters the nucleus, which correlates with hyperphosphorylation of C/EBPβ and acquisition of DNA-binding activity. Concurrently, 3T3-L1 preadipocytes synchronously enter S phase and undergo mitotic clonal expansion, a prerequisite for terminal differentiation. Ex vivo and in vitro experiments with C/EBPβ show that phosphorylation of Thr-188 by mitogen-activating protein kinase “primes” C/EBPβ for subsequent phosphorylation on Ser-184 and Thr-179 by glycogen synthase kinase 3β, acquisition of DNA-binding function, and transactivation of the C/EBPα and PPARγ genes. The delayed transactivation of the C/EBPα and PPARγ genes by C/EBPβ appears necessary to allow mitotic clonal expansion, which would otherwise be prevented, because C/EBPα and PPARγ are antimitotic.

Bibliography

Tang, Q.-Q., GrÃ¸nborg, M., Huang, H., Kim, J.-W., Otto, T. C., Pandey, A., & Lane, M. D. (2005). Sequential phosphorylation of CCAAT enhancer-binding protein Î² by MAPK and glycogen synthase kinase 3Î² is required for adipogenesis. Proceedings of the National Academy of Sciences, 102(28), 9766â9771.

Authors 7

Qi-Qun Tang (first)
Mads Grønborg (additional)
Haiyan Huang (additional)
Jae-Woo Kim (additional)
Tamara C. Otto (additional)
Akhilesh Pandey (additional)
M. Daniel Lane (additional)

References 30 Referenced 277

Dates

Type	When
Created	20 years, 2 months ago (June 29, 2005, 12:42 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:20 p.m.)
Indexed	1 month, 4 weeks ago (July 2, 2025, 2:32 p.m.)
Issued	20 years, 2 months ago (June 28, 2005)
Published	20 years, 2 months ago (June 28, 2005)
Published Online	20 years, 2 months ago (June 28, 2005)
Published Print	20 years, 1 month ago (July 12, 2005)

Funders 0

None

BibTeX

@article{Tang_2005, title={Sequential phosphorylation of CCAAT enhancer-binding protein β by MAPK and glycogen synthase kinase 3β is required for adipogenesis}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0503891102}, DOI={10.1073/pnas.0503891102}, number={28}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Tang, Qi-Qun and Grønborg, Mads and Huang, Haiyan and Kim, Jae-Woo and Otto, Tamara C. and Pandey, Akhilesh and Lane, M. Daniel}, year={2005}, month=jun, pages={9766–9771} }

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  "abstract": "<jats:p>\n            CCAAT enhancer-binding protein (C/EBP)\u03b2, C/EBP\u03b1, and peroxisome proliferator activated receptor (PPAR)\u03b3 act in a cascade where C/EBP\u03b2 activates expression of C/EBP\u03b1 and PPAR\u03b3, which then function as pleiotropic activators of genes that produce the adipocyte phenotype. When growth-arrested 3T3-L1 preadipocytes are induced to differentiate, C/EBP\u03b2 is rapidly expressed but still lacks DNA-binding activity. After a long (14-hour) lag, glycogen synthase kinase 3\u03b2 enters the nucleus, which correlates with hyperphosphorylation of C/EBP\u03b2 and acquisition of DNA-binding activity. Concurrently, 3T3-L1 preadipocytes synchronously enter S phase and undergo mitotic clonal expansion, a prerequisite for terminal differentiation.\n            <jats:italic>Ex vivo</jats:italic>\n            and\n            <jats:italic>in vitro</jats:italic>\n            experiments with C/EBP\u03b2 show that phosphorylation of Thr-188 by mitogen-activating protein kinase \u201cprimes\u201d C/EBP\u03b2 for subsequent phosphorylation on Ser-184 and Thr-179 by glycogen synthase kinase 3\u03b2, acquisition of DNA-binding function, and transactivation of the C/EBP\u03b1 and PPAR\u03b3 genes. The delayed transactivation of the C/EBP\u03b1 and PPAR\u03b3 genes by C/EBP\u03b2 appears necessary to allow mitotic clonal expansion, which would otherwise be prevented, because C/EBP\u03b1 and PPAR\u03b3 are antimitotic.\n          </jats:p>",
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