QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Philpott, A Articles by Tsai, L H Search for Related Content PubMed PubMed Citation Articles by Philpott, A Articles by Tsai, L H Social Bookmarking                   What's this?

Research Papers

The role of cyclin-dependent kinase 5 and a novel regulatory subunit in regulating muscle differentiation and patterning.

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. philpott@bcmp.med.harvard.edu

Abstract

Cyclin-dependent kinase 5, coupled with its activator p35, is required for normal neuronal differentiation and patterning. We have isolated a novel member of the p35 family, Xp35.1, from Xenopus embryos which can activate cdk5. Xp35.1 is expressed in both proliferating and differentiated neural and mesodermal cells and is particularly high in developing somites where cdk5 is also expressed. Using dominant-negative cdk5 (cdk5 DN), we show that cdk5 kinase activity is required for normal somitic muscle development; expression of cdk5 DN results in disruption of somitic muscle patterning, accompanied by stunting of the embryos. Using explants of animal pole tissue from blastula embryos, which will differentiate into mesoderm in response to activin, we show that blocking cdk5 kinase activity down-regulates the expression of the muscle marker muscle actin in response to activin, whereas the pan-mesodermal marker Xbra is unaffected. Expression of MyoD and MRF4 (master regulators of myogenesis) is suppressed in the presence of cdk5 DN, indicating that these myogenic genes may be a target for cdk5 regulation, whereas the related factor Myf5 is largely unaffected. In addition, overexpression of Xp35.1 disrupts muscle organization. Thus, we have demonstrated a novel role for cdk5 in regulating myogenesis in the early embryo.

CiteULike

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Movassagh and A. Philpott Cardiac differentiation in Xenopus requires the cyclin-dependent kinase inhibitor, p27Xic1 Cardiovasc Res, August 1, 2008; 79(3): 436 - 447. [Abstract] [Full Text] [PDF]

				L. G. Puente, S. Voisin, R. E. C. Lee, and L. A. Megeney Reconstructing the Regulatory Kinase Pathways of Myogenesis from Phosphopeptide Data Mol. Cell. Proteomics, December 1, 2006; 5(12): 2244 - 2251. [Abstract] [Full Text] [PDF]

				G. Ren, P. Vajjhala, J. S. Lee, B. Winsor, and A. L. Munn The BAR Domain Proteins: Molding Membranes in Fission, Fusion, and Phagy Microbiol. Mol. Biol. Rev., March 1, 2006; 70(1): 37 - 120. [Abstract] [Full Text] [PDF]

				C. Y. Gao, M. A. Stepp, R. Fariss, and P. Zelenka Cdk5 regulates activation and localization of Src during corneal epithelial wound closure J. Cell Sci., August 15, 2004; 117(18): 4089 - 4098. [Abstract] [Full Text] [PDF]

				L. Richard-Parpaillon, R. A. Cosgrove, C. Devine, A. E. Vernon, and A. Philpott G1/S phase cyclin-dependent kinase overexpression perturbs early development and delays tissue-specific differentiation in Xenopus Development, June 1, 2004; 131(11): 2577 - 2586. [Abstract] [Full Text] [PDF]

				A. K. Y. Fu, W.-Y. Fu, A. K. Y. Ng, W. W. Y. Chien, Y.-P. Ng, J. H. Wang, and N. Y. Ip Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity PNAS, April 27, 2004; 101(17): 6728 - 6733. [Abstract] [Full Text] [PDF]

				K. Alexander, H.-S. Yang, and P. W. Hinds Cellular Senescence Requires CDK5 Repression of Rac1 Activity Mol. Cell. Biol., April 1, 2004; 24(7): 2808 - 2819. [Abstract] [Full Text] [PDF]

				C. M. Sahlgren, A. Mikhailov, S. Vaittinen, H.-M. Pallari, H. Kalimo, H. C. Pant, and J. E. Eriksson Cdk5 Regulates the Organization of Nestin and Its Association with p35 Mol. Cell. Biol., July 15, 2003; 23(14): 5090 - 5106. [Abstract] [Full Text] [PDF]

				Y.-l. Zheng, B.-S. Li, Veeranna, and H. C. Pant Phosphorylation of the Head Domain of Neurofilament Protein (NF-M): A FACTOR REGULATING TOPOGRAPHIC PHOSPHORYLATION OF NF-M TAIL DOMAIN KSP SITES IN NEURONS J. Biol. Chem., June 20, 2003; 278(26): 24026 - 24032. [Abstract] [Full Text] [PDF]

				C. Gao, S. Negash, H. T. Guo, D. Ledee, H.-S. Wang, and P. Zelenka CDK5 Regulates Cell Adhesion and Migration in Corneal Epithelial Cells Mol. Cancer Res., November 1, 2002; 1(1): 12 - 24. [Abstract] [Full Text] [PDF]

				S. Negash, H.-S. Wang, C. Gao, D. Ledee, and P. Zelenka Cdk5 regulates cell-matrix and cell-cell adhesion in lens epithelial cells J. Cell Sci., May 15, 2002; 115(10): 2109 - 2117. [Abstract] [Full Text] [PDF]

				P. Sharma, Veeranna, M. Sharma, N. D. Amin, R. K. Sihag, P. Grant, N. Ahn, A. B. Kulkarni, and H. C. Pant Phosphorylation of MEK1 by cdk5/p35 Down-regulates the Mitogen-activated Protein Kinase Pathway J. Biol. Chem., January 4, 2002; 277(1): 528 - 534. [Abstract] [Full Text]

				Y. Iuchi, T. Kobayashi, T. Kaneko, M. Takahara, T. Ogino, and J. Fujii Expression of a Y-box protein, YB2/RYB-a, precedes protamine 2 expression during spermatogenesis in rodents Mol. Hum. Reprod., November 1, 2001; 7(11): 1023 - 1031. [Abstract] [Full Text] [PDF]

				D. S. Smith, P. L. Greer, and L.-H. Tsai Cdk5 on the Brain Cell Growth Differ., June 1, 2001; 12(6): 277 - 283. [Abstract] [Full Text] [PDF]

				A. Catania, S. Urban, E. Yan, C. Hao, G. Barron, and J. Allalunis-Turner Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells Neuro-oncol, April 1, 2001; 3(2): 89 - 98. [Abstract] [PDF]

				T. Tanaka, Veeranna, T. Ohshima, P. Rajan, N. D. Amin, A. Cho, T. Sreenath, H. C. Pant, R. O. Brady, and A. B. Kulkarni Neuronal Cyclin-Dependent Kinase 5 Activity Is Critical for Survival J. Neurosci., January 15, 2001; 21(2): 550 - 558. [Abstract] [Full Text] [PDF]

				C Gao, S Negash, H. Wang, D Ledee, H Guo, P Russell, and P Zelenka Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock J. Cell Sci., January 3, 2001; 114(6): 1145 - 1153. [Abstract] [PDF]

				S Humbert, R Dhavan, and L Tsai p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton J. Cell Sci., January 3, 2000; 113(6): 975 - 983. [Abstract] [PDF]

				S. Nakano, I. Akiguchi, S. Nakamura, H. Satoi, S. Kawashima, and J. Kimura Aberrant expression of cyclin-dependent kinase 5 in inclusion body myositis Neurology, November 1, 1999; 53(8): 1671 - 1671. [Abstract] [Full Text] [PDF]

				W. A. Wilson, A. M. Mahrenholz, and P. J. Roach Substrate Targeting of the Yeast Cyclin-Dependent Kinase Pho85p by the Cyclin Pcl10p Mol. Cell. Biol., October 1, 1999; 19(10): 7020 - 7030. [Abstract] [Full Text] [PDF]

				M. L. Ruchhoeft, S.-i. Ohnuma, L. McNeill, C. E. Holt, and W. A. Harris The Neuronal Architecture of Xenopus Retinal Ganglion Cells Is Sculpted by Rho-Family GTPases In Vivo J. Neurosci., October 1, 1999; 19(19): 8454 - 8463. [Abstract] [Full Text] [PDF]

				K.-T. Chin, S.-y. Ohki, D. Tang, H.-C. Cheng, J. H. Wang, and M. Zhang Identification and Structure Characterization of a Cdk Inhibitory Peptide Derived from Neuronal-specific Cdk5 Activator J. Biol. Chem., March 12, 1999; 274(11): 7120 - 7127. [Abstract] [Full Text] [PDF]

				J.-M. Li and G. Brooks Cell cycle regulatory molecules (cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors) and the cardiovascular system; potential targets for therapy? Eur. Heart J., March 2, 1999; 20(6): 406 - 420. [PDF]

				G. N. Patrick, P. Zhou, Y. T. Kwon, P. M. Howley, and L.-H. Tsai p35, the Neuronal-specific Activator of Cyclin-dependent Kinase 5 (Cdk5) Is Degraded by the Ubiquitin-Proteasome Pathway J. Biol. Chem., September 11, 1998; 273(37): 24057 - 24064. [Abstract] [Full Text] [PDF]

				H. H. Shih, S. G. Tevosian, and A. S. Yee Regulation of Differentiation by HBP1, a Target of the Retinoblastoma Protein Mol. Cell. Biol., August 1, 1998; 18(8): 4732 - 4743. [Abstract] [Full Text]

				K. M. Grant, P. Hassan, J. S. Anderson, and J. C. Mottram The crk3 Gene of Leishmania mexicana Encodes a Stage-regulated cdc2-related Histone H1 Kinase That Associates with p12cks1 J. Biol. Chem., April 24, 1998; 273(17): 10153 - 10159. [Abstract] [Full Text] [PDF]

				S. R. Floyd, E. B. Porro, V. I. Slepnev, G.-C. Ochoa, L.-H. Tsai, and P. De Camilli Amphiphysin 1 Binds the Cyclin-dependent Kinase (cdk) 5 Regulatory Subunit p35 and Is Phosphorylated by cdk5 and cdc2 J. Biol. Chem., March 9, 2001; 276(11): 8104 - 8110. [Abstract] [Full Text] [PDF]

				C. M. Sahlgren, A. Mikhailov, J. Hellman, Y.-H. Chou, U. Lendahl, R. D. Goldman, and J. E. Eriksson Mitotic Reorganization of the Intermediate Filament Protein Nestin Involves Phosphorylation by cdc2 Kinase J. Biol. Chem., May 4, 2001; 276(19): 16456 - 16463. [Abstract] [Full Text] [PDF]

				K.-x. Huang and H. K. Paudel Ser67-phosphorylated inhibitor 1 is a potent protein phosphatase 1 inhibitor PNAS, May 23, 2000; 97(11): 5824 - 5829. [Abstract] [Full Text] [PDF]