![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vol. 13, Issue 11, 4013-4028, November 2002
and§
Protein kinases of the microtubule affinity-regulating kinase
(MARK) family were originally discovered because of their ability to
phosphorylate certain sites in tau protein (KXGS motifs in the repeat
domain). This type of phosphorylation is enhanced in abnormal tau from
Alzheimer brain tissue and causes the detachment of tau from
microtubules. MARK-related kinases (PAR-1 and KIN1) occur in various
organisms and are involved in establishing and maintaining cell
polarity. Herein, we report the ability of MARK2 to affect the
differentiation and outgrowth of cell processes from neuroblastoma and
other cell models. MARK2 phosphorylates tau protein at the KXGS motifs;
this results in the detachment of tau from microtubules and their
destabilization. The formation of neurites in N2a cells is blocked if
MARK2 is inactivated, either by transfecting a dominant negative
mutant, or by MARK2 inhibitors such as hymenialdisine. Alternatively,
neurites are blocked if the target KXGS motifs on tau are rendered
nonphosphorylatable by point mutations. The results suggest that MARK2
contributes to the plasticity of microtubules needed for neuronal
polarity and the growth of neurites.
Max-Planck-Unit for Structural Molecular Biology,
Hamburg, Germany; and Centre National de la Recherche
Scientifique, Station Biologique, F-29682 Roscoff, France
This article has been cited by other articles:
|
|
 |
|
  T. Timm, K. Balusamy, X. Li, J. Biernat, E. Mandelkow, and E.-M. Mandelkow Glycogen Synthase Kinase (GSK) 3{beta} Directly Phosphorylates Serine 212 in the Regulatory Loop and Inhibits Microtubule Affinity-regulating Kinase (MARK) 2 J. Biol. Chem., July 4, 2008; 283(27): 18873 - 18882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Flynn, E. T. Maizels, A. B. Karlsson, T. McAvoy, J.-H. Ahn, A. C. Nairn, and M. Hunzicker-Dunn Luteinizing Hormone Receptor Activation in Ovarian Granulosa Cells Promotes Protein Kinase A-Dependent Dephosphorylation of Microtubule-Associated Protein 2D Mol. Endocrinol., July 1, 2008; 22(7): 1695 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sapir, S. Sapoznik, T. Levy, D. Finkelshtein, A. Shmueli, T. Timm, E.-M. Mandelkow, and O. Reiner Accurate Balance of the Polarity Kinase MARK2/Par-1 Is Required for Proper Cortical Neuronal Migration J. Neurosci., May 28, 2008; 28(22): 5710 - 5720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Johne, D. Matenia, X.-y. Li, T. Timm, K. Balusamy, and E.-M. Mandelkow Spred1 and TESK1--Two New Interaction Partners of the Kinase MARKK/TAO1 That Link the Microtubule and Actin Cytoskeleton Mol. Biol. Cell, April 1, 2008; 19(4): 1391 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. V. Uboha, M. Flajolet, A. C. Nairn, and M. R. Picciotto A Calcium- and Calmodulin-Dependent Kinase I{alpha}/Microtubule Affinity Regulating Kinase 2 Signaling Cascade Mediates Calcium-Dependent Neurite Outgrowth J. Neurosci., April 18, 2007; 27(16): 4413 - 4423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Hurov, M. Huang, L. S. White, J. Lennerz, C. S. Choi, Y.-R. Cho, H.-J. Kim, J. L. Prior, D. Piwnica-Worms, L. C. Cantley, et al. Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo PNAS, March 27, 2007; 104(13): 5680 - 5685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Thies and E.-M. Mandelkow Missorting of Tau in Neurons Causes Degeneration of Synapses That Can Be Rescued by the Kinase MARK2/Par-1 J. Neurosci., March 14, 2007; 27(11): 2896 - 2907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Sharma, J. M. Litersky, K. Bhaskar, and G. Lee Tau impacts on growth-factor-stimulated actin remodeling J. Cell Sci., March 1, 2007; 120(5): 748 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. McKinsey Derepression of pathological cardiac genes by members of the CaM kinase superfamily Cardiovasc Res, March 1, 2007; 73(4): 667 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Wang, Y. Imai, and B. Lu Activation of PAR-1 Kinase and Stimulation of Tau Phosphorylation by Diverse Signals Require the Tumor Suppressor Protein LKB1 J. Neurosci., January 17, 2007; 27(3): 574 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Hung, C. Hwang, M. D. Po, and M. Zhen Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans Development, January 15, 2007; 134(2): 237 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Goransson, M. Deak, S. Wullschleger, N. A. Morrice, A. R. Prescott, and D. R. Alessi Regulation of the polarity kinases PAR-1/MARK by 14-3-3 interaction and phosphorylation J. Cell Sci., October 1, 2006; 119(19): 4059 - 4070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Marx, C. Nugoor, J. Muller, S. Panneerselvam, T. Timm, M. Bilang, E. Mylonas, D. I. Svergun, E.-M. Mandelkow, and E. Mandelkow Structural Variations in the Catalytic and Ubiquitin-associated Domains of Microtubule-associated Protein/Microtubule Affinity Regulating Kinase (MARK) 1 and MARK2 J. Biol. Chem., September 15, 2006; 281(37): 27586 - 27599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Chen, Q. J. Wang, H. S. Hu, P. C. Yu, J. Zhu, G. Drewes, H. Piwnica-Worms, and Z. G. Luo Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity PNAS, May 30, 2006; 103(22): 8534 - 8539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Khlistunova, J. Biernat, Y. Wang, M. Pickhardt, M. von Bergen, Z. Gazova, E. Mandelkow, and E.-M. Mandelkow Inducible Expression of Tau Repeat Domain in Cell Models of Tauopathy: AGGREGATION IS TOXIC TO CELLS BUT CAN BE REVERSED BY INHIBITOR DRUGS J. Biol. Chem., January 13, 2006; 281(2): 1205 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kosuga, E. Tashiro, T. Kajioka, M. Ueki, Y. Shimizu, and M. Imoto GSK-3beta Directly Phosphorylates and Activates MARK2/PAR-1 J. Biol. Chem., December 30, 2005; 280(52): 42715 - 42722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Margolis and J.-P. Borg Apicobasal polarity complexes J. Cell Sci., November 15, 2005; 118(22): 5157 - 5159. [Full Text] [PDF]
|
|
|
|
|
|
D. Matenia, B. Griesshaber, X.-y. Li, A. Thiessen, C. Johne, J. Jiao, E. Mandelkow, and E.-M. Mandelkow PAK5 Kinase Is an Inhibitor of MARK/Par-1, Which Leads to Stable Microtubules and Dynamic Actin Mol. Biol. Cell, September 1, 2005; 16(9): 4410 - 4422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Darios, M.-P. Muriel, M. E. Khondiker, A. Brice, and M. Ruberg Neurotoxic Calcium Transfer from Endoplasmic Reticulum to Mitochondria Is Regulated by Cyclin-Dependent Kinase 5-Dependent Phosphorylation of Tau J. Neurosci., April 20, 2005; 25(16): 4159 - 4168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kishi, Y. A. Pan, J. G. Crump, and J. R. Sanes Mammalian SAD Kinases Are Required for Neuronal Polarization Science, February 11, 2005; 307(5711): 929 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Boudeau, J. W. Scott, N. Resta, M. Deak, A. Kieloch, D. Komander, D. G. Hardie, A. R. Prescott, D. M. F. van Aalten, and D. R. Alessi Analysis of the LKB1-STRAD-MO25 complex J. Cell Sci., December 15, 2004; 117(26): 6365 - 6375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. V. W. Johnson and W. H. Stoothoff Tau phosphorylation in neuronal cell function and dysfunction J. Cell Sci., November 15, 2004; 117(24): 5721 - 5729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.-M. Mandelkow, E. Thies, B. Trinczek, J. Biernat, and E. Mandelkow MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons J. Cell Biol., October 11, 2004; 167(1): 99 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Caenepeel, G. Charydczak, S. Sudarsanam, T. Hunter, and G. Manning The mouse kinome: Discovery and comparative genomics of all mouse protein kinases PNAS, August 10, 2004; 101(32): 11707 - 11712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cohen, P. J. Brennwald, E. Rodriguez-Boulan, and A. Musch Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton J. Cell Biol., March 1, 2004; 164(5): 717 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Trinczek, M. Brajenovic, A. Ebneth, and G. Drewes MARK4 Is a Novel Microtubule-associated Proteins/Microtubule Affinity-regulating Kinase That Binds to the Cellular Microtubule Network and to Centrosomes J. Biol. Chem., February 13, 2004; 279(7): 5915 - 5923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Goldberg How does an axon grow? Genes & Dev., April 15, 2003; 17(8): 941 - 958. [Full Text] [PDF]
|
|
