PMID- 25015294
OWN - NLM
STAT- MEDLINE
DCOM- 20150622
LR  - 20211021
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 127
IP  - Pt 18
DP  - 2014 Sep 15
TI  - Divergent and convergent roles for kinases and phosphatases in neurofilament 
      dynamics.
PG  - 4064-77
LID - 10.1242/jcs.153346 [doi]
AB  - C-terminal neurofilament phosphorylation mediates cation-dependent 
      self-association leading to neurofilament incorporation into the stationary 
      axonal cytoskeleton. Multiple kinases phosphorylate the C-terminal domains of the 
      heavy neurofilament subunit (NF-H), including cyclin-dependent protein kinase 5 
      (CDK5), mitogen-activated protein kinases (MAPKs), casein kinase 1 and 2 (CK1 and 
      CK2) and glycogen synthase kinase 3beta (GSK3beta). The respective contributions of 
      these kinases have been confounded because they phosphorylate multiple substrates 
      in addition to neurofilaments and display extensive interaction. Herein, 
      differentiated NB2a/d1 cells were transfected with constructs expressing 
      GFP-tagged NF-H, isolated NF-H sidearms and NF-H lacking the distal-most 187 
      amino acids. Cultures were treated with roscovitine, PD98059, Li(+), D4476, 
      tetrabromobenzotriazole and calyculin, which are active against CDK5, MKK1 (also 
      known as MAP2K1), GSK3beta, CK1, CK2 and protein phosphatase 1 (PP1), respectively. 
      Sequential phosphorylation by CDK5 and GSK3beta mediated the 
      neurofilament-neurofilament associations. The MAPK pathway (i.e. MKK1 to ERK1/2) 
      was found to downregulate GSK3beta, and CK1 activated PP1, both of which promoted 
      axonal transport and restricted neurofilament-neurofilament associations to 
      axonal neurites. The MAPK pathway and CDK5, but not CK1 and GSK3beta, inhibited 
      neurofilament proteolysis. These findings indicate that phosphorylation of 
      neurofilaments by the proline-directed MAPK pathway and CDK5 counterbalance the 
      impact of phosphorylation of neurofilaments by the non-proline-directed CK1 and 
      GSK3beta.
CI  - (c) 2014. Published by The Company of Biologists Ltd.
FAU - Lee, Sangmook
AU  - Lee S
AD  - Center for Cellular Neurobiology and Neurodegeneration Research, Department of 
      Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA 
      sangmook_lee@uml.edu PantH@ninds.nih.gov thomas_shea@uml.edu.
FAU - Pant, Harish C
AU  - Pant HC
AD  - Cytoskeletal Protein Regulation Section, NIH, NINDS, Bethesda, MD 20892, USA 
      sangmook_lee@uml.edu PantH@ninds.nih.gov thomas_shea@uml.edu.
FAU - Shea, Thomas B
AU  - Shea TB
AD  - Center for Cellular Neurobiology and Neurodegeneration Research, Department of 
      Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA 
      sangmook_lee@uml.edu PantH@ninds.nih.gov thomas_shea@uml.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140711
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Casein Kinase I)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
SB  - IM
MH  - Animals
MH  - Axonal Transport
MH  - Axons/enzymology
MH  - Casein Kinase I/genetics/metabolism
MH  - Casein Kinase II/genetics/metabolism
MH  - Cell Line, Tumor
MH  - Glycogen Synthase Kinase 3/genetics/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Intermediate Filaments/*enzymology/genetics
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
MH  - Phosphoprotein Phosphatases/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/genetics/*metabolism
PMC - PMC6519427
OTO - NOTNLM
OT  - Axonal stability
OT  - Cytoskeleton
OT  - Kinase
OT  - Neurofilament
OT  - Phosphatase
EDAT- 2014/07/13 06:00
MHDA- 2015/06/24 06:00
PMCR- 2014/09/14
CRDT- 2014/07/13 06:00
PHST- 2014/07/13 06:00 [entrez]
PHST- 2014/07/13 06:00 [pubmed]
PHST- 2015/06/24 06:00 [medline]
PHST- 2014/09/14 00:00 [pmc-release]
AID - jcs.153346 [pii]
AID - 10.1242/jcs.153346 [doi]
PST - ppublish
SO  - J Cell Sci. 2014 Sep 15;127(Pt 18):4064-77. doi: 10.1242/jcs.153346. Epub 2014 
      Jul 11.