Recombinant Mouse Muscle, skeletal receptor tyrosine-protein kinase (Musk),Partial

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Code CSB-EP730715MO
Size US$306
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP730715MO could indicate that this peptide derived from E.coli-expressed Mus musculus (Mouse) Musk.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP730715MO could indicate that this peptide derived from E.coli-expressed Mus musculus (Mouse) Musk.
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Product Details

Purity
Greater than 90% as determined by SDS-PAGE.
Target Names
Musk
Uniprot No.
Research Area
Signal Transduction
Alternative Names
Musk; Nsk2; Muscle; skeletal receptor tyrosine-protein kinase; EC 2.7.10.1; Muscle-specific tyrosine-protein kinase receptor; MuSK; Muscle-specific kinase receptor
Species
Mus musculus (Mouse)
Source
E.coli
Expression Region
22-494aa
Target Protein Sequence
EKLPKAPVITTPLETVDALVEEVATFMCAVESYPQPEISWTRNKILIKLFDTRYSIRENGQLLTILSVEDSDDGIYCCIANNGVGGAVESCGALQVKMKPKITRPPINVKIIEGLKAVLPCTTMGNPKPSVSWIKGDNALRENSRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGTAYSKLVKLEVEVFARILRAPESHNVTFGSFVTLRCTAIGIPVPTISWIENGNAVSSGSIQESVKDRVIDSRLQLFITKPGLYTCIATNKHGEKFSTAKAAATVSIAEWSKSQKDSQGYCAQYRGEVCDAVLAKDALVFFNTSYRDPEDAQELLIHTAWNELKAVSPLCRPAAEALLCNHLFQECSPGVVPTPMPICREYCLAVKELFCAKEWQAMEGKAHRGLYRSGMHLLPVPECSKLPSMHRDPTACTRLPYLDYKKENITTFPSITSSRPSADIPNLPASTSSFAVSPAYSMT
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
69.3kDa
Protein Length
Extracellular Domain
Tag Info
N-terminal 10xHis-SUMO-tagged and C-terminal Myc-tagged
Form
Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer
Tris-based buffer,50% glycerol
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
3-7 business days
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA
Please contact us to get it.
Description

The Recombinant Mouse Musk protein is a protein encoded by recombinant DNA that was cloned in an expression vector that supported the expression of Musk gene. This recombinant Musk protein was expressed in the host. The expression region is 22-494aa of the Mouse Musk. In the production, the expression vector contains N-terminal 10xHis-SUMO tag and C-terminal Myc tag. Every production step was performed with a strict QC system. The purity of this protein is 90%+ determined by SDS-PAGE.

The receptor tyrosine kinase MuSK (muscle-specific kinase) is the key signaling molecule during the formation of a mature and functional neuromuscular junction (NMJ). Signal transduction events downstream of MuSK activation induce both pre- and postsynaptic differentiation, which, most prominently, includes the clustering of acetylcholine receptors at synaptic sites. MuSK originally described as Trk-related receptor tyrosine kinase (RTK) in the electric organ of Torpedo californica, was isolated as a novel RTK from denervated mouse muscle and termed muscle-specific kinase due to its prominent expression in skeletal muscle. MuSK activation requires a complex interplay between its coreceptor Lrp4 (low-density lipoprotein receptor-related protein-4), the motor neuron-derived heparan-sulfate proteoglycan Agrin and the intracellular adaptor protein Dok-7. A tight regulation of MuSK kinase activity is crucial for proper NMJ development. Defects in MuSK signaling are the cause of muscle weakness as reported in congenital myasthenic syndromes and myasthenia gravis. Of note, recently it was shown that MuSK acts as coreceptor of bone morphogenic proteins in myoblasts to stimulate the expression of a distinct set of genes linking MuSK to pathways involved in muscle differentiation and growth.

 

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Target Background

Function
Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle. Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation.
Gene References into Functions
  1. Gene expression profiling showed that MuSK was required for the BMP4-induced expression of a subset of genes in myoblasts, including regulator of G protein signaling 4 (Rgs4). PMID: 27601729
  2. These mice showed only marginal activation of MuSK and died by 3 weeks of age apparently due to an abnormally small number and size of neuromuscular junction (NMJs). PMID: 28069867
  3. data reveal that muscle skeletal receptor tyrosine kinase cysteine-rich domain is critical for neuromuscular junction formation and plays an unsuspected role in NMJ maintenance in adulthood. PMID: 25810523
  4. Forced expression of Dok-7 in muscle enhanced MuSK activation in mice lacking agrin or Lrp4 and restored midmuscle NMJ formation in agrin-deficient mice, but not in Lrp4-deficient mice. PMID: 25368159
  5. pathogenic IgG4 antibodies to MuSK bind to a structural epitope in the first Ig-like domain of MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK phosphorylation. PMID: 24297891
  6. MuSK colocalizes with actin and Arf6 at the cell surface and during endosomal trafficking. PMID: 23621612
  7. Increasing MuSK activity delays denervation and improves motor function in ALS mice. PMID: 22939980
  8. Two classic synaptic signalling systems (neuregulin-1 and neural agrin) converge upon MuSK to regulate postsynaptic differentiation. PMID: 22328506
  9. Biglycan binding to MuSK rescues the unstable acetylcholine receptor clusters that are involved in neuromuscular junction formation and postsynaptic differentiation. PMID: 22396407
  10. Data suggest that adult skeletal muscles harbour different endogenous levels of MuSK and that these levels determine the ability to form ectopic AChR clusters upon overexpression of agrin or MuSK. PMID: 21255125
  11. Depletion of MuSK at the neuromuscular junction leads to disassembly of muscle-specific kinase and muscle weakness of myasthenia gravis in mice. PMID: 20603331
  12. Data show that expression of a chimeric receptor containing the juxtamembrane region of Musk and the kinase domain of TrkA restores presynaptic and postsynaptic differentiation in Musk-deficient mice. PMID: 12403715
  13. Activation of a musk promoter reporter construct in muscle fibers in vivo and in cultured myotubes, using transfection of multiple combinations of expression vectors for potential signaling components PMID: 12756238
  14. analysis of regulation of MuSK expression by a novel signaling pathway PMID: 12885777
  15. Our results suggest that muscle tyrosine phosphatases tightly regulate MuSK activation and signaling and support a novel role of Shp2 in MuSK-dependent AChR clustering. PMID: 15737732
  16. Musk expression was inhibited by CREB interacting with a CRE-like element with MyoD. PMID: 15964791
  17. Our findings demonstrate that MuSK kinase activity is required throughout postnatal development to hold up MuSK and AChR levels at endplates. PMID: 16337809
  18. A low-molecular weight isoform of muscle-specific receptor tyrosine kinase in mouse sperm localized in the flagellar mid-piece region of human sperm. PMID: 16487930
  19. These results demonstrate a novel pathway linking the NO-soluble guanylyl cyclase-cGMP pathway, SR Ca2+ release, PLB, and CaM kinase II to relaxation in gastric fundus smooth muscles. PMID: 16510846
  20. Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK PMID: 16794080
  21. muscle-specific receptor tyrosine kinase activation and binding to dystroglycan are regulated by alternative mRNA splicing of agrin PMID: 17012237
  22. A new member of the Shc family of docking proteins is characterised, which may mediate a specific aspect of signaling downstream of the MuSK receptor. PMID: 17452444
  23. MuSK controls where motor axons grow and form synapses. PMID: 18084289
  24. the COOH-terminal NES and Src homology 2 target motifs play key roles in Dok-7/MuSK signaling for neuromuscular synaptogenesis. PMID: 18165682
  25. The IGg1/2 domain of MuSK is involved in acetylcholine receptor clustering by binding to the muscle surface. PMID: 18253062
  26. Our study reveals a potentially novel mechanism that regulates agrin/MuSK signaling cascade. PMID: 18272689
  27. adult musk(V789M/-) mice show severe muscle weakness; diaphragm exhibits pronounced changes in endplate architecture, distribution & innervation; missense mutation V789M in MuSK acts as a hypomorphic mutation & leads to insufficiency in MuSK function PMID: 18718936
  28. These experiments indicate that Lrp4 is the long-sought and elusive receptor for Agrin and has a critical role in activating MuSK and stimulating neuromuscular synapse formation. PMID: 18848351

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Subcellular Location
Cell junction, synapse, postsynaptic cell membrane; Single-pass type I membrane protein. Note=Localizes to the postsynaptic cell membrane of the neuromuscular junction.
Protein Families
Protein kinase superfamily, Tyr protein kinase family
Tissue Specificity
Expressed preferentially in skeletal muscle.
Database Links
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