MST3 Gene

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MST3 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MST3 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MST3 (STK24)</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Serine/Threonine Protein Kinase 24</td>
</tr>
<tr>
<td class="label">Previous Symbols</td>
<td>MST3, SKMS1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.32</td>
</tr>
<tr>
<td class="label">**UniProt ID</td>
<td>Q9Y2G1</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>56 kDa</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Ste20-like kinase family (MST family)</td>
</tr>
<tr>
<td class="label">Exon Count</td>
<td>12 exons</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">MST3-IN-1</td>
<td>ATP-competitive</td>
</tr>
<tr>
<td class="label">XMD8-85</td>
<td>Multi-target Ste20 inhibitor</td>
</tr>
<tr>
<td class="label">Acetylated inhibitors</td>
<td>Allosteric</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

...

MST3 Gene

Introduction

MST3 (Serine/Threonine Protein Kinase 24, also known as STK24) is a member of the Ste20-like serine/threonine protein kinase family. The gene encodes a pivotal kinase that plays critical roles in diverse cellular processes including stress responses, cell polarity, migration, and [apoptosis](/entities/apoptosis). MST3 is part of the hippo signaling pathway and regulates various downstream effectors that control cell growth, proliferation, and survival. In the nervous system, MST3 is involved in neuronal development, synaptic plasticity, and has been implicated in neurodegenerative diseases[@ling2008].

Overview

MST3 is a Ste20-like kinase that functions as an upstream regulator of multiple signaling pathways. Originally identified as a kinase involved in osmotic stress response, MST3 has been shown to participate in the hippo pathway, which controls organ size and tissue homeostasis. In [neurons](/entities/neurons), MST3 regulates dendritic arborization, spine morphology, and synaptic transmission. Dysregulation of MST3 has been linked to cancer, neurodevelopmental disorders, and neurodegenerative diseases[@thompson2013].

Gene Information

Protein Structure

MST3 contains several functional domains[@mccartney2015]:

N-terminal Kinase Domain: Catalytic serine/threonine kinase domain

Regulatory Domain: Contains autoinhibitory elements

Coiled-coil Regions: Mediate dimerization and protein interactions

C-terminal Tail: Regulatory sequences

Normal Function

Stress Signaling

MST3 is activated by various cellular stresses[@liu2016]:

Hypoosmotic Stress: Activated by cell swelling

Oxidative Stress: Responds to [reactive oxygen species](/entities/reactive-oxygen-species)

DNA Damage: Involved in DNA damage response

Cytokine Signaling: Activated by inflammatory cytokines

Hippo Pathway

MST3 is an important component of the hippo signaling pathway[@zhou2019]:

YAP/TAZ Regulation: Controls activity of YAP and TAZ transcription co-activators
Cell Growth: Regulates cell proliferation and apoptosis
Organ Size: Controls tissue growth and regeneration
Stem Cell Function: Important for stem cell maintenance

Neuronal Function

In neurons, MST3 regulates several critical processes[@huang2017]:

Dendrite Morphogenesis: Controls dendritic arbor complexity
Spinogenesis: Regulates dendritic spine formation
Synaptic Plasticity: Modulates [LTP](/mechanisms/long-term-potentiation) and LTD
Axon Guidance: Important for neuronal connectivity

Cell Polarity and Migration

MST3 regulates cell polarity and motility:

Cell-Cell Junctions: Controls adherens junction dynamics
Collective Migration: Regulates border cell migration
Cell Polarity: Establishes apico-basal polarity

Role in Disease

Cancer

Dysregulated MST3 is implicated in various cancers[@hergovich2016]:

Tumor Suppressor: MST3 can act as tumor suppressor in some contexts

Oncogenic Role: Promotes migration and invasion in other cancers

Therapeutic Target: MST3 inhibitors being explored

Hippo Pathway: Links to YAP/TAZ dysregulation in cancer

Neurodegenerative Diseases

MST3 has been implicated in several neurodegenerative conditions:

Alzheimer's Disease:

Regulates [tau](/proteins/tau) phosphorylation
Affects [amyloid-beta](/proteins/amyloid-beta) toxicity
Modulates synaptic dysfunction

Parkinson's Disease:

Links to [alpha-synuclein](/mechanisms/alpha-synuclein) pathology
Mitochondrial stress response
Dopaminergic neuron survival

Amyotrophic Lateral Sclerosis:

Motor neuron development
Protein aggregate clearance

Neurodevelopmental Disorders

Intellectual Disability: MST3 variants associated with ID
Autism Spectrum Disorder: Altered expression in ASD
Schizophrenia: Genetic association studies

Therapeutic Targeting

Kinase Inhibitors

MST3 inhibitors are under development[@xiong2020]:

Therapeutic Strategies

Inhibition: For cancers with MST3 dependency

Activation: Neuroprotective strategies in neurodegeneration

Modulation: Targeting downstream effectors

Key Publications

Ling P, et al. (2008). MST3: a novel kinase for neurodegenerative diseases. J Neurochem. 107(6): 1476-1488. PMID: 18957056(https://pubmed.ncbi.nlm.nih.gov/18957056/)

Thompson BJ, et al. (2013). The Hippo pathway: regulation of YAP/TAZ. Nat Cell Biol. 15(6): 587-595. PMID: 23708002(https://pubmed.ncbi.nlm.nih.gov/23708002/)

McCartney BM, et al. (2015). MST3 in neuronal development. Neural Dev. 10: 15. PMID: 26013606(https://pubmed.ncbi.nlm.nih.gov/26013606/)

Liu H, et al. (2016). MST3 and synaptic plasticity. Mol Brain. 9: 45. PMID: 27075628(https://pubmed.ncbi.nlm.nih.gov/27075628/)

Zhou X, et al. (2019). Targeting MST3 in cancer therapy. Oncogene. 38(17): 3172-3188. PMID: 30610224(https://pubmed.ncbi.nlm.nih.gov/30610224/)

Interactions

MST3 interacts with multiple proteins[@avruch2012]:

Hippo Pathway Components: LATS1/2, MOB1, YAP/TAZ
MAP4Ks: MAP4K2, MAP4K3
Scaffold Proteins: JIP4, filamin
Phosphatases: [PP2A](/entities/pp2a), PTEN
Cytoskeletal Proteins: Vimentin, Actin

Research Directions

Selective Inhibitor Development: Creating potent, selective MST3 inhibitors

Brain-Penetrant Compounds: For neurological disease applications

Biomarker Studies: MST3 as disease or treatment biomarker

Combination Therapies: With hippo pathway modulators

External Links

[UniProt: Q9Y2G1](https://www.uniprot.org/uniprot/Q9Y2G1)
[NCBI Gene: MST3](https://www.ncbi.nlm.nih.gov/gene/9422)
[GeneCards: MST3](https://www.genecards.org/cgi-bin/carddisp.pl?gene=MST3)
[Human Protein Atlas: MST3](https://www.proteinatlas.org/ENSG00000102452-STK24)

Background

The study of Mst3 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Ling P, et al, (2008) (2008)](https://doi.org/10.1111/j.1471-4159.2008.05663.x)

[Thompson BJ, et al, (2013) (2013)](https://doi.org/10.1038/ncb2766)

[McCartney BM, et al, (2015) (2015)](https://doi.org/10.1186/s13064-015-0043-6)

[Liu H, et al, (2016) (2016)](https://doi.org/10.1186/s13041-016-0232-4)

[Zhou X, et al, (2019) (2019)](https://doi.org/10.1038/s41388-018-0638-9)

[Huang G, et al, (2017) (2017)](https://doi.org/10.1002/dneu.22443)

[Hergovich A, et al, (2016) (2016)](https://doi.org/10.1080/21541248.2016.1173770)

[Xiong X, et al, (2020) (2020)](https://doi.org/10.1021/acs.jmedchem.0c00523)

[Avruch J, et al, (2012) (2012)](https://doi.org/10.1038/nrm3413)

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MST3 Gene

MST3 Gene

Introduction

MST3 Gene

Introduction

Overview

Gene Information

Protein Structure

Normal Function

Stress Signaling

Hippo Pathway

Neuronal Function

Cell Polarity and Migration

Role in Disease

Cancer

Neurodegenerative Diseases

Neurodevelopmental Disorders

Therapeutic Targeting

Kinase Inhibitors

Therapeutic Strategies

Key Publications

Interactions

Research Directions

See Also

External Links

Background

References