PMID- 11461155
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20211203
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 18
IP  - 1
DP  - 2001 Jul
TI  - Regulation of alternative splicing of human tau exon 10 by phosphorylation of 
      splicing factors.
PG  - 80-90
AB  - Tau is a microtubule-associated protein whose transcript undergoes regulated 
      splicing in the mammalian nervous system. Exon 10 of the gene is an alternatively 
      spliced cassette that is adult-specific and encodes a microtubule-binding domain. 
      Mutations increasing the inclusion of exon 10 result in the production of tau 
      protein which predominantly contains four microtubule-binding repeats and were 
      shown to cause frontotemporal dementia and parkinsonism linked to chromosome 17 
      (FTDP-17). Here we show that exon 10 usage is regulated by CDC2-like kinases 
      CLK1, 2, 3, and 4 that phosphorylate serine-arginine-rich proteins, which in turn 
      regulate pre-mRNA splicing. Cotransfection experiments suggest that CLKs achieve 
      this effect by releasing specific proteins from nuclear storage sites. Our 
      results show that changing pre-mRNA-processing pathways through phosphorylation 
      could be a new therapeutic concept for tauopathies.
CI  - Copyright 2001 Academic Press.
FAU - Hartmann, A M
AU  - Hartmann AM
AD  - Max Planck Institute of Neurobiology, Am Klopferspitz 18a, Martinsried, D-82152, 
      Germany.
FAU - Rujescu, D
AU  - Rujescu D
FAU - Giannakouros, T
AU  - Giannakouros T
FAU - Nikolakaki, E
AU  - Nikolakaki E
FAU - Goedert, M
AU  - Goedert M
FAU - Mandelkow, E M
AU  - Mandelkow EM
FAU - Gao, Q S
AU  - Gao QS
FAU - Andreadis, A
AU  - Andreadis A
FAU - Stamm, S
AU  - Stamm S
LA  - eng
GR  - R01-AG18486/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (MAPT protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA Precursors)
RN  - 0 (tau Proteins)
RN  - EC 2.7.1.- (Clk dual-specificity kinases)
RN  - EC 2.7.1.- (SRPK1 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDK5 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Alternative Splicing/*physiology
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Cell Line
MH  - Cyclin-Dependent Kinase 5
MH  - Cyclin-Dependent Kinases/metabolism
MH  - Exons
MH  - Humans
MH  - Kidney/cytology
MH  - Microtubule-Associated Proteins/genetics
MH  - Molecular Sequence Data
MH  - Mutagenesis/physiology
MH  - Nuclear Proteins/*genetics/*metabolism
MH  - Phosphorylation
MH  - Point Mutation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - RNA Precursors/genetics
MH  - Transfection
MH  - tau Proteins/*genetics
EDAT- 2001/07/20 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/07/20 10:00
PHST- 2001/07/20 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/07/20 10:00 [entrez]
AID - S1044-7431(01)91000-0 [pii]
AID - 10.1006/mcne.2001.1000 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2001 Jul;18(1):80-90. doi: 10.1006/mcne.2001.1000.