PMID- 36608736
OWN - NLM
STAT- MEDLINE
DCOM- 20230210
LR  - 20240501
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 104
DP  - 2023 Apr
TI  - From phosphorylation to phenotype - Recent key findings on kinase regulation, 
      downstream signaling and disease surrounding the receptor tyrosine kinase MuSK.
PG  - 110584
LID - S0898-6568(22)00346-1 [pii]
LID - 10.1016/j.cellsig.2022.110584 [doi]
AB  - Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction 
      development. MuSK acts via several distinct pathways and is responsible for pre- 
      and postsynaptic differentiation. MuSK is unique among receptor tyrosine kinases 
      as activation and signaling are particularly tightly regulated. Initiation of 
      kinase activity requires Agrin, a heparan sulphate proteoglycan derived from 
      motor neurons, the low-density lipoprotein receptor-related protein-4 (Lrp4) and 
      the intracellular adaptor protein Dok-7. There is a great knowledge gap between 
      MuSK activation and downstream signaling. Recent studies using omics techniques 
      have addressed this knowledge gap, thereby greatly contributing to a better 
      understanding of MuSK signaling. Impaired MuSK signaling causes severe muscle 
      weakness as described in congenital myasthenic syndromes or myasthenia gravis but 
      the underlying pathophysiology is often unclear. This review focuses on recent 
      advances in deciphering MuSK activation and downstream signaling. We further 
      highlight latest break-throughs in understanding and treatment of MuSK-related 
      disorders and discuss the role of MuSK in non-muscle tissue.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Promer, Jakob
AU  - Promer J
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Barresi, Cinzia
AU  - Barresi C
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Herbst, Ruth
AU  - Herbst R
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria. Electronic address: ruth.herbst@meduniwien.ac.at.
LA  - eng
GR  - DOC 33/FWF_/Austrian Science Fund FWF/Austria
GR  - P 31199/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230103
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (Muscle Proteins)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Phosphorylation
MH  - *Neuromuscular Junction/genetics/metabolism
MH  - *Receptors, Cholinergic/genetics/metabolism
MH  - LDL-Receptor Related Proteins/genetics
MH  - Muscle Proteins/metabolism
MH  - Receptor Protein-Tyrosine Kinases/metabolism
OTO - NOTNLM
OT  - Agrin
OT  - MuSK
OT  - Neuromuscular disorders
OT  - Neuromuscular junction
OT  - Skeletal muscle
COIS- Declaration of Competing Interest The authors declare no competing financial or 
      non-financial interests.
EDAT- 2023/01/08 06:00
MHDA- 2023/02/11 06:00
CRDT- 2023/01/07 16:02
PHST- 2022/11/18 00:00 [received]
PHST- 2022/12/16 00:00 [revised]
PHST- 2022/12/31 00:00 [accepted]
PHST- 2023/01/08 06:00 [pubmed]
PHST- 2023/02/11 06:00 [medline]
PHST- 2023/01/07 16:02 [entrez]
AID - S0898-6568(22)00346-1 [pii]
AID - 10.1016/j.cellsig.2022.110584 [doi]
PST - ppublish
SO  - Cell Signal. 2023 Apr;104:110584. doi: 10.1016/j.cellsig.2022.110584. Epub 2023 
      Jan 3.