Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Satellite Stem Cells and Muscular Dystrophy01:21

Satellite Stem Cells and Muscular Dystrophy

Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Lipids regulate epidermal growth factor receptor activation by its ligands.

Biochemical Society transactions·2026
Same author

The role of kinase domain dimerization in EGFR activation.

Structure (London, England : 1993)·2025
Same author

MuSK is a substrate for CaMK2β but this interaction is dispensable for MuSK activation in vivo.

Scientific reports·2025
Same author

Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS.

Nature communications·2025
Same author

Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling.

eLife·2024
Same author

Building, Breaking, and Repairing Neuromuscular Synapses.

Cold Spring Harbor perspectives in biology·2024
Same journal

Mechanistic insights into acetylated histone recognition by the CECR2 bromodomain.

The Biochemical journal·2026
Same journal

Nanobodies against Plasmodium adhesins that block receptor engagement and malaria parasite invasion.

The Biochemical journal·2026
Same journal

Persistence without turnover: the RhoG G12E mutant highlights the role of nucleotide cycling in RhoG signaling.

The Biochemical journal·2026
Same journal

Alternative Splicing of Rice Chloroplastic CuZn Superoxide Dismutase, OsCSD2: Impact on expression and protein characteristics.

The Biochemical journal·2026
Same journal

Difference and similarity between the ubiquitous secretory pathway Ca2+-ATPases, SERCA2b, and SPCA1a.

The Biochemical journal·2026
Same journal

A molecular perspective on dimethylarginine dimethylaminohydrolases structure and function.

The Biochemical journal·2026
See all related articles

Related Experiment Video

Updated: Jun 5, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

An S752D activation loop mutation dynamically primes Muscle-Specific Kinase for activation.

Jakob J Prömer1,2,3, James W Murphy2,3, Mark A Lemmon2,3

  • 1Institute for Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

The Biochemical Journal
|June 4, 2026
PubMed
Summary
This summary is machine-generated.

Phosphorylation of serine 752 in muscle-specific kinase (MuSK) primes it for activation by increasing flexibility and stabilizing signaling interactions. This research clarifies MuSK regulation at the neuromuscular junction.

Keywords:
A-loop autoinhibitionhydrogen-deuterium exchange mass spectrometrymuscle-specific kinaseneuromuscular junctionreceptor tyrosine kinases

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Related Experiment Videos

Last Updated: Jun 5, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Neuroscience

Background:

  • Muscle-specific kinase (MuSK) is crucial for neuromuscular junction (NMJ) formation and function.
  • MuSK's autoinhibited state, stabilized by activation loop (A-loop) tyrosines, presents a barrier to understanding its regulation.
  • Previous work suggested A-loop serine phosphorylation might prime MuSK for activation.

Purpose of the Study:

  • To investigate the role of A-loop serine phosphorylation in MuSK activation.
  • To elucidate the structural and dynamic changes associated with MuSK autoinhibition relief.
  • To provide a mechanistic framework for MuSK regulation at the NMJ.

Main Methods:

  • X-ray crystallography to determine MuSK structures.
  • Biochemical assays to measure enzyme activity and binding affinity.
  • Hydrogen-deuterium exchange and mass spectrometry (HDX-MS) to assess protein dynamics.

Main Results:

  • A phosphomimetic S752D mutation disrupted autoinhibitory interactions, increasing ATP binding and catalytic turnover.
  • HDX-MS revealed the S752D mutation enhances A-loop flexibility, relieving autoinhibition.
  • The S752D mutation stabilized the juxtamembrane NPXY motif, a key site for Dok7 interaction.

Conclusions:

  • A-loop serine phosphorylation acts as a priming mechanism for MuSK activation.
  • Dynamic transitions in the A-loop and JM region are critical for relieving MuSK autoinhibition.
  • These findings offer insights into the molecular mechanisms governing MuSK signaling at the NMJ.