PMID- 27666825
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Sep 26
TI  - MuSK Kinase Activity is Modulated By A Serine Phosphorylation Site in The Kinase 
      Loop.
PG  - 33583
LID - 10.1038/srep33583 [doi]
LID - 33583
AB  - The neuromuscular junction (NMJ) forms when a motor neuron contacts a muscle 
      fibre. A reciprocal exchange of signals initiates a cascade of signalling events 
      that result in pre- and postsynaptic differentiation. At the centre of these 
      signalling events stands muscle specific kinase (MuSK). MuSK activation, kinase 
      activity and subsequent downstream signalling are crucial for NMJ formation as 
      well as maintenance. Therefore MuSK kinase activity is tightly regulated to 
      ensure proper NMJ development. We have identified a novel serine phosphorylation 
      site at position 751 in MuSK that is increasingly phosphorylated upon agrin 
      stimulation. S751 is also phosphorylated in muscle tissue and its phosphorylation 
      depends on MuSK kinase activity. A phosphomimetic mutant of S751 increases MuSK 
      kinase activity in response to non-saturating agrin concentrations . In addition, 
      basal MuSK and AChR phosphorylation as well as AChR cluster size are increased. 
      We believe that the phosphorylation of S751 provides a novel mechanism to relief 
      the autoinhibition of the MuSK activation loop. Such a lower autoinhibition could 
      foster or stabilize MuSK kinase activation, especially during stages when no or 
      low level of agrin are present. Phosphorylation of S751 might therefore represent 
      a novel mechanism to modulate MuSK kinase activity during prepatterning or NMJ 
      maintenance.
FAU - Camurdanoglu, B Z
AU  - Camurdanoglu BZ
AD  - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 
      Vienna, Austria.
FAU - Hrovat, C
AU  - Hrovat C
AD  - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 
      Vienna, Austria.
FAU - Durnberger, G
AU  - Durnberger G
AD  - Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
AD  - Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, 
      Austria.
AD  - Gregor Mendel Institute (GMI), Austrian Academy of Sciences, Vienna Biocenter 
      (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
FAU - Madalinski, M
AU  - Madalinski M
AD  - Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
AD  - Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, 
      Austria.
FAU - Mechtler, K
AU  - Mechtler K
AD  - Institute for Molecular Pathology (IMP), Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
AD  - Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, 
      Austria.
FAU - Herbst, R
AU  - Herbst R
AD  - Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 
      Vienna, Austria.
AD  - Institute of Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 
      Vienna, Austria.
LA  - eng
PT  - Journal Article
DEP - 20160926
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
EIN - Sci Rep. 2016 Dec 01;6:38271. PMID: 27905551
PMC - PMC5035991
EDAT- 2016/09/27 06:00
MHDA- 2016/09/27 06:01
PMCR- 2016/09/26
CRDT- 2016/09/27 06:00
PHST- 2016/04/27 00:00 [received]
PHST- 2016/08/31 00:00 [accepted]
PHST- 2016/09/27 06:00 [entrez]
PHST- 2016/09/27 06:00 [pubmed]
PHST- 2016/09/27 06:01 [medline]
PHST- 2016/09/26 00:00 [pmc-release]
AID - srep33583 [pii]
AID - 10.1038/srep33583 [doi]
PST - epublish
SO  - Sci Rep. 2016 Sep 26;6:33583. doi: 10.1038/srep33583.