PAK2 Protein — p21-Activated Kinase 2
<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">PAK2 Protein (p21-Activated Kinase 2)</th></tr>
<tr><td><strong>Protein Name</strong></td><td>p21-Activated Kinase 2</td></tr>
<tr><td><strong>Gene</strong></td><td>[PAK2](/genes/pak2)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q13153](https://www.uniprot.org/uniprot/Q13153)</td></tr>
<tr><td><strong>PDB ID</strong></td><td>1E0K, 3P4I, 1E0T</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~58 kDa (524 amino acids)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, Membrane, Nucleus</td></tr>
<tr><td><strong>Protein Family</strong></td><td>PAK (p21-activated kinase) family</td></tr>
<tr><td><strong>Enzyme Classification</strong></td><td>Serine/Threonine Kinase</td></tr>
</table>
</div>
Overview
PAK2 (p21-Activated Kinase 2) is a serine/threonine kinase that serves as a critical effector of the Rho GTPases RAC1 and CDC42. As a member of the Group I PAK family (alongside [PAK1](/proteins/pak1-protein) and [PAK3](/proteins/pak3-protein)), PAK2 plays diverse roles in cytoskeletal reorganization, cell adhesion, synaptic plasticity, and apoptotic signaling. In the context of neurodegenerative diseases, PAK2 has emerged as an important regulator of [tau](/proteins/tau) phosphorylation, dendritic spine morphology, and neuronal survival. This page provides a comprehensive overview of PAK2's structure, normal physiological functions, and its role in Alzheimer's disease, Parkinson's disease, and related disorders.
Introduction
The p21-activated kinases (PAKs) represent a family of serine/threonine kinases that function as downstream effectors of small GTPases, particularly RAC1 and CDC42[@bokoch2003]. These proteins were originally identified as binding partners for the small GTPases p21^ras^ and p21^rac^, hence the name "p21-activated kinases"[@manser1998]. The PAK family is divided into two groups: Group I (PAK1, PAK2, PAK3) and Group II (PAK4, PAK5, PAK6). PAK2 is ubiquitously expressed and plays distinct roles in various tissues, including the nervous system.
In neurons, PAK2 is involved in critical processes such as dendritic spine formation, synaptic plasticity, and axonal guidance[@penzes2010]. Dysregulation of PAK2 signaling has been implicated in multiple neurodegenerative conditions, with particular emphasis on its role in [Alzheimer's disease](/diseases/alzheimers-disease)[@zhao2006][@ma2008]. The kinase participates in pathways that regulate [tau](/proteins/tau) phosphorylation, amyloid-beta toxicity, and synaptic dysfunction — all hallmark features of Alzheimer's disease pathogenesis.
Understanding PAK2's role in neurodegeneration has become increasingly important due to its potential as a therapeutic target. Recent studies have explored PAK inhibitors as potential disease-modifying agents for Alzheimer's disease[@yang2025], highlighting the translational relevance of this protein in neurotherapeutics.
Structure
PAK2 possesses a characteristic domain architecture that enables its regulation through multiple mechanisms:
Domain Organization
PAK2 contains approximately 524 amino acids with the following structural features:
N-terminal Regulatory Domain: Contains the p21-binding domain (PBD) and an autoinhibitory region (ARI). The PBD (residues 67-91) mediates binding to active RAC1 and CDC42 GTPases. The autoinhibitory domain (residues 92-127) folds onto the kinase domain to maintain inactivity in the basal state[@lei2000].
Proline-Rich Region: Contains SH3-binding motifs that facilitate interactions with adaptor proteins such as Nck and Crk.
Kinase Domain: Located at the C-terminus (residues 132-473), this catalytic domain phosphorylates numerous substrates on serine/threonine residues. The kinase domain adopts a typical bilobal structure common to eukaryotic protein kinases.
C-terminal Regulatory Tail: Contains additional phosphorylation sites that modulate kinase activity.Autoinhibition and Activation
Full-length PAK2 exists in an autoinhibited conformation where the N-terminal regulatory domain interacts with the kinase domain, blocking substrate access[@lei2000]. Activation occurs through two primary mechanisms:
GTPase-Dependent Activation: Binding of GTP-bound RAC1 or CDC42 to the PBD disrupts the autoinhibitory interaction, leading to kinase activation.
Proteolytic Activation: During [apoptosis](/entities/apoptosis), caspase-3 cleaves PAK2 at Asp212, generating a constitutively active fragment (PAK2-C) that lacks the regulatory domain[@jakobi2005]. This cleaved form promotes apoptotic signaling.Structural Studies
Crystal structures of PAK2 have revealed the molecular basis of autoinhibition and provided insights for inhibitor development. The PDB structures 1E0K and 1E0T represent the kinase domain in inactive and active conformations, respectively. These structural studies have informed the development of ATP-competitive PAK inhibitors such as IPA-3 and FRAX597.
Normal Function
In the healthy nervous system, PAK2 participates in numerous cellular processes essential for neuronal development and function:
Cytoskeletal Dynamics
PAK2 is a key regulator of actin and microtubule cytoskeleton through its effects on downstream effectors including LIMK1, cofilin, and myosin light chain[@daniels1999]. Key functions include:
- Actin Polymerization: PAK2 phosphorylates and activates LIMK1, which in turn phosphorylates cofilin, inhibiting its actin-depolymerizing activity. This promotes actin filament stability and enables formation of lamellipodia and filopodia.
- Microtubule Dynamics: PAK2 interacts with tubulin and regulates microtubule organization in neurons[@kesavapany2007]. This function is particularly important for axonal guidance and dendritic branching.
- Cell Adhesion: Through effects on focal adhesion kinase (FAK) and paxillin, PAK2 regulates integrin-mediated cell-matrix adhesion and neuronal migration[@zhang2005].
Synaptic Plasticity
PAK2 plays critical roles in synaptic structure and function[@hayashi2004]:
- Dendritic Spine Morphogenesis: PAK2 regulates the formation, maintenance, and remodeling of dendritic spines — the postsynaptic sites of most excitatory synapses. PAK2 activity influences spine shape, size, and density through actin cytoskeleton remodeling.
- Synaptic Transmission: PAK2 is involved in presynaptic vesicle trafficking and neurotransmitter release[@huber2014]. The protein localizes to synaptic terminals where it regulates the cycling of synaptic vesicles.
- Long-term Potentiation (LTP): PAK signaling is required for LTP, the cellular basis of learning and memory. PAK activity is necessary for AMPA receptor trafficking during LTP.
Neuronal Development
During development, PAK2 contributes to:
- Neuronal Migration: PAK2 coordinates actin dynamics during neuronal migration from ventricular zones to their final positions[@zhang2005].
- Axon Guidance: PAK2 mediates repulsive axon guidance in response to extracellular cues such as semaphorins.
- Dendrite Arborization: PAK2 regulates the branching and elaboration of dendritic trees.
Cell Survival and Apoptosis
The dual nature of PAK2 function is exemplified in its regulation of cell survival[@jakobi2005]:
- Pro-survival Signaling: In its full-length form, PAK2 promotes cell survival through NF-κB activation and AKT signaling.
- Pro-apoptotic Signaling: Upon apoptotic stimuli, caspase-mediated cleavage generates PAK2-C, which translocates to the nucleus and promotes apoptotic gene expression[@salomoni2010].
DNA Damage Response
Nuclear PAK2 participates in DNA damage response pathways, phosphorylating checkpoint kinases and promoting DNA repair. This function is particularly relevant in post-mitotic neurons, which are particularly vulnerable to DNA damage accumulation.
Role in Neurodegenerative Diseases
Alzheimer's Disease
PAK2 has been implicated in multiple aspects of Alzheimer's disease pathogenesis:
Tau Phosphorylation
PAK2 directly and indirectly regulates [tau](/proteins/tau) phosphorylation through several mechanisms[@whiteman2009][@kesavapany2007]:
- PAK2 phosphorylates tau at multiple sites, including Thr181, Ser202, and Thr231
- PAK2 activates GSK-3β, a major tau kinase
- PAK2-LIMK1-cofilin pathway dysregulation affects tau pathology
- In AD brain, PAK2 is abnormally activated and shows altered subcellular distribution[@ma2008]
Synaptic Dysfunction
The PAK pathway is significantly affected in Alzheimer's disease[@zhao2006][@bories2017]:
- PAK1/2 signaling deficits contribute to cognitive deficits
- Group I PAK activity is reduced in AD hippocampus
- PAK dysfunction leads to dendritic spine loss
- Transgenic autoinhibition of PAK exacerbates synaptic impairments in AD mouse models
- PAK1 inhibition preserves dendritic spines in amyloid/tau-exposed neurons[@yang2025]
Therapeutic Implications
PAK modulators represent potential therapeutic strategies for AD:
- PAK1/2 activators may protect synapses
- PAK inhibitors may reduce pathological tau phosphorylation
- The LIMK1-cofilin axis is a downstream target affected in sporadic AD[@sollazzo2024]
Parkinson's Disease
While less studied than in Alzheimer's disease, PAK2 involvement in [Parkinson's disease](/diseases/parkinsons-disease) includes:
Dopaminergic Neuron Survival
PAK2 plays a role in the survival of dopaminergic neurons in the substantia nigra:
- PAK2 activity promotes pro-survival signaling through Akt and NF-κB pathways
- In PD models, PAK2 dysregulation contributes to apoptotic cell death
- PAK2 cleavage (generating the pro-apoptotic PAK2-C fragment) is increased in 6-OHDA and MPTP models
Alpha-Synuclein Toxicity
PAK2 interacts with [alpha-synuclein](/proteins/alpha-synuclein) pathology:
- PAK2 phosphorylation of synphilin-1 modulates α-synuclein aggregation
- PAK2 activity is altered in synucleinopathies
- PAK2 may participate in the cellular response to Lewy body formation
Mitochondrial Dynamics
PAK2 regulates mitochondrial function:
- PAK2 participates in mitochondrial fission through interactions with Drp1
- PAK2 dysfunction leads to mitochondrial fragmentation
- Mitochondrial deficits in PD may involve PAK2 dysregulation
LRRK2 Interaction
The [LRRK2](/genes/lrrk2) (leucine-rich repeat kinase 2) protein, a major PD gene product, may intersect with PAK2 signaling:
- Both LRRK2 and PAK2 are serine/threonine kinases
- Potential convergence on cytoskeletal regulation
- May explain shared phenotypes in model systems
Other Neurodegenerative Conditions
PAK2 dysregulation has been implicated in:
- Huntington's Disease: PAK2 activity affects mutant huntingtin aggregation and toxicity
- Amyotrophic Lateral Sclerosis (ALS): Alterations in PAK signaling in motor neurons
- Intellectual Disability: PAK3 mutations cause X-linked intellectual disability[@cau2018]; PAK2 may have compensatory functions
- Stroke and Brain Injury: PAK2 participates in excitotoxic and ischemic damage
Therapeutic Targeting
PAK2 represents a compelling therapeutic target for neurodegenerative diseases, with multiple strategies under investigation:
PAK Inhibitors
Several PAK inhibitors have been developed and tested in preclinical models[@fischer2017]:
| Compound | Specificity | Development Stage | Key Findings |
|----------|-------------|-------------------|--------------|
| IPA-3 | PAK1/2 (Group I) | Preclinical | First selective PAK inhibitor; blocks tumor cell invasion; improves synaptic function in AD models |
| FRAX597 | PAK1/2/3 | Preclinical | Reduces glioma growth; inhibits pathological tau phosphorylation; CNS penetration demonstrated |
| G-5555 | PAK1 | Preclinical | Improved cardiac function; potential for CNS applications; good oral bioavailability |
| PF-3758309 | PAK4 | Phase I (oncology) | First PAK inhibitor in clinical trials; defines safety profile for the class |
| APS-2-147 | PAK1/2 | Preclinical | Dual PAK/Aurora kinase inhibitor; being developed for AD |
| EHT-5372 | PAK2/3 | Preclinical | Brain-penetrant PAK inhibitor with neuroprotective properties |
IPA-3 (P21-Activated Kinase Inhibitor 3)
IPA-3 is a selective, covalent inhibitor of Group I PAKs (PAK1, PAK2, PAK3):
- Mechanism: Covalent modification of a cysteine residue in the PAK1/2 kinase domain
- IC50: ~200 nM for PAK1, ~400 nM for PAK2
- In vivo: Improves learning and memory in APP/PS1 mice
- Limitations: Metabolic instability; requires parenteral administration
FRAX597
FRAX597 is a potent, ATP-competitive inhibitor of PAK1/2/3:
- Demonstrated brain penetration in mouse models
- Reduces tau phosphorylation in neuronal cultures
- Improves synaptic function in AD models
- Being developed by Forrest Laboratories for CNS applications
PAK Activators (Pro-Synaptic Strategy)
Rather than inhibiting PAK, a complementary strategy involves activating PAK to protect synapses:
- Cell-permeable PAK peptides: Designed to disrupt autoinhibition without causing constitutive activation
- RAC1 activators: Upstream activation of the PAK pathway through small molecules that promote RAC1-GTP loading
- Gene therapy: Viral delivery of constitutively active PAK2 constructs to specific brain regions
Challenges and Opportunities
Therapeutic targeting of PAK2 faces several challenges:
Isoform Specificity: Developing inhibitors that specifically target PAK2 versus other isoforms. The kinase domains of Group I PAKs are highly conserved. Strategies include targeting unique allosteric sites or using covalent modification of non-conserved cysteine residues.
Biphasic Effects: PAK2 has both pro-survival and pro-apoptotic functions; complete inhibition may be detrimental. The full-length kinase promotes cell survival while the cleaved fragment promotes apoptosis. Therapeutic window requires careful titration.
Blood-Brain Barrier: CNS penetration required for neurological applications. Many PAK inhibitors have poor brain exposure. Strategies include:
- Design of new molecules with improved passive diffusion
- Use of active transport mechanisms (e.g., LAT1 transporters)
- Intranasal delivery approaches
- Focused ultrasound-mediated BBB opening
Timing of Intervention: Optimal window for therapeutic intervention may vary by disease stage. In prodromal AD, PAK activation may be beneficial; in later stages, inhibition of pathological PAK2 cleavage may be preferred.Combination Therapies
PAK-targeting strategies may be most effective in combination:
- PAK modulators + Aβ-targeting agents: Combined anti-amyloid and pro-synapse strategies
- PAK + GSK-3β inhibitors: Target both upstream (PAK) and downstream (GSK-3β) tau kinases
- PAK + NMDA receptor modulators: Synergistic effects on synaptic plasticity
Clinical Trial Considerations
Translating PAK-targeting therapies to clinical use requires:
- Biomarker development to identify patients most likely to benefit
- Establishment of pharmacodynamic endpoints (e.g., PAK activity in peripheral blood mononuclear cells)
- Careful monitoring for potential off-target effects
- Long-term safety studies given the chronic nature of neurodegenerative diseases
Future Directions
Emerging strategies include:
- Allosteric PAK2 modulators: Greater specificity through targeting unique allosteric sites
- Targeted delivery: Nanoparticles or antibody conjugates for brain-specific delivery
- Gene therapy: AAV-mediated expression of modified PAK2 for sustained modulation
- Combination approaches: Integration with existing AD therapeutics
- Personalized medicine: Genetic stratification based on PAK pathway polymorphisms
Clinical-Stage PAK Inhibitors
| Agent | Company | Indication | Phase | Status |
|-------|---------|------------|-------|--------|
| PF-3758309 | Pfizer | Solid tumors | Phase I | Completed; no further development |
| FRAX597 | Forrest Labs | Glioma/AD | Preclinical | IND-enabling studies |
| G-5555 | G1 Therapeutics | Multiple | Preclinical | Partnership with Pfizer |
While no PAK inhibitors have reached clinical testing for neurodegenerative indications, the existing oncology data provide safety and pharmacokinetic insights that accelerate CNS drug development.
Interacting Proteins and Pathways
PAK2 participates in numerous protein-protein interactions that mediate its diverse cellular functions:
Direct Interactors
GTPases
- RAC1: Primary physiological activator; binding to active RAC1-GTP relieves autoinhibition and activates PAK2 kinase activity. RAC1-PAK2 signaling regulates actin dynamics, cell adhesion, and synaptic plasticity.
- CDC42: Functions similarly to RAC1 as a PAK2 activator. CDC42-PAK2 signaling is particularly important for filopodia formation, cell polarity, and mitotic spindle orientation.
- R-Ras: Can activate PAK2 with distinct functional outcomes compared to RAC1/CDC42.
Adaptor Proteins
- NCK1/NCK2: SH2/SH3 domain-containing adaptors that link PAK2 to activated receptor tyrosine kinases. Nck binding recruits PAK2 to membrane ruffles and leading edges.
- CRK: Binds to PAK2 proline-rich regions; mediates integrin signaling and cell migration.
- GRB2: Links PAK2 to growth factor receptor signaling.
Downstream Effectors
- LIMK1: PAK2 directly phosphorylates and activates LIMK1, which in turn phosphorylates cofilin. This cascade regulates actin filament dynamics[@sollazzo2024].
- Moesin: PAK2 phosphorylates ezrin-radixin-moesin (ERM) proteins, linking actin to plasma membrane.
- Myosin Light Chain (MLC): PAK2 phosphorylates MLC, regulating actomyosin contractility.
- p120-catenin: PAK2 phosphorylation affects adherens junction dynamics.
Kinases and Phosphatases
- Akt/PKB: Bidirectional relationship — Akt phosphorylates PAK2, regulating its activity; PAK2 can phosphorylate Akt substrates.
- PKA: Phosphorylates PAK2 on distinct sites, often with opposing effects to RAC1 binding.
- PKC: Multiple isoforms regulate PAK2 through phosphorylation.
- PP1 (Protein Phosphatase 1): Dephosphorylates PAK2 to regulate its activity cycle.
Signaling Pathways
PAK2 interfaces with multiple signaling cascades:
Rho GTPase Signaling: Central effector of RAC1/CDC42; integrates upstream GTPase signals into diverse cellular responses[@banerjee2009].
MAPK Pathways:
- ERK1/2 activation by PAK2 promotes cell survival and proliferation
- PAK2 can activate JNK and p38, linking stress signals to cytoskeletal regulation
PI3K/Akt Survival Pathway: PAK2 contributes to Akt-mediated pro-survival signaling through multiple mechanisms.
NF-κB Pathway: PAK2 activation leads to IKK activation and NF-κB nuclear translocation, promoting inflammatory gene expression.
DNA Damage Response: Nuclear PAK2 phosphorylates ATM and ATR substrates, promoting cell cycle checkpoint activation and DNA repair[@salomoni2010].
Wnt/β-catenin Pathway: PAK2 can modulate β-catenin degradation and transcriptional activity.
Hedgehog Signaling: Cross-talk between PAK2 and GLI transcription factors.
Notch Pathway: PAK2 affects Notch processing and signaling.Subcellular Localization
PAK2 localization is dynamically regulated:
- Cytoplasmic: Inactive pool in quiescent cells
- Membrane: Activated PAK2 at plasma membrane ruffles and focal adhesions
- Nuclear: Active PAK2-C fragment translocates to nucleus
- Golgi: Participates in vesicular transport
- Mitochondria: Associated with mitochondrial dynamics
- Synaptic terminals: Presynaptic and postsynaptic localization
The dynamic localization enables context-specific signaling and substrate access.
Animal Models and Experimental Findings
Knockout Models
PAK2 knockout studies have revealed critical insights into its physiological functions:
- PAK2 null mice: Embryonic lethal around E9.5-E10.5; mice die due to defects in cytokinesis and cell proliferation. This early lethality demonstrates the essential role of PAK2 in early development[@lei2000].
- Conditional brain-specific knockout: Deletion of PAK2 in the central nervous system leads to:
- Reduced dendritic complexity in cortical neurons
- Impaired synaptic plasticity and learning deficits
- Altered spine morphology with reduced spine density
- Increased susceptibility to excitotoxic injury
- Double PAK1/PAK2 knockout: Combined deletion produces severe neurodevelopmental phenotypes:
- Profound defects in neuronal migration
- Failure to form proper cortical layering
- Early postnatal lethality
- Severe deficits in axon guidance and connectivity
- Heterozygous PAK2 mice: Partial reduction shows:
- Subtle cognitive deficits
- Reduced LTP in hippocampal slices
- Altered stress responses
- Phenotypes exacerbated with age
Transgenic Models
Several transgenic models have been developed to study PAK2 in disease contexts:
- PAK2 autoinhibitory transgene: Expressing a dominant-negative PAK2 (PAK2-KR) in neurons recapitulates AD synaptic deficits[@bories2017]:
- Reduced dendritic spine density in hippocampus
- Impaired contextual fear memory
- Exacerbated amyloid pathology in APP/PS1 mice
- Fronto-dependent behavioral deficits
- PAK2-C (cleaved) overexpression: Modeling the pro-apoptotic cleavage product:
- Promotes neuronal apoptosis in vitro and in vivo
- Activates caspase-3 and DNA fragmentation
- Translocates to nucleus to promote pro-apoptotic gene expression
- Model for excitotoxic and ischemic brain injury
- PAK2-CA (constitutively active) models:
- Constitutively active PAK2 promotes dendritic spine formation
- May enhance synaptic function but also increases aberrant connectivity
- Effects vary by brain region and developmental stage
- APP/PAK double transgenic models:
- Cross of APP/PS1 with PAK2 modulatory transgenes
- Used to test therapeutic modulation of PAK signaling
- PAK inhibition reduces amyloid-induced spine loss
Key Experimental Findings
Numerous experimental findings support the importance of PAK2 in neurodegeneration:
PAK activity is reduced in AD brain: Post-mortem studies show significantly reduced Group I PAK activity in hippocampus and cortex of AD patients compared to age-matched controls.
Paky mice show AD-like phenotypes: Genetic mouse models with reduced PAK activity exhibit learning and memory deficits similar to early AD.
Restoring PAK signaling improves function: Viral-mediated delivery of active PAK improves synaptic function and cognition in aged or AD model mice.
PAK2 cleavage correlates with disease severity: Levels of the cleaved (active) PAK2 fragment increase with disease progression in AD brain, correlating with tangle density and cognitive decline.
PAK in fluid biomarkers: PAK2 and downstream signaling molecules are detectable in cerebrospinal fluid and may serve as biomarkers for synaptic dysfunction in AD.
Sex-specific effects: PAK2 expression and activity show sex-specific patterns, potentially explaining some of the female bias in AD prevalence.Key Publications
[Zhao L, et al. (2006). PAK pathway defects contribute to cognitive deficits in Alzheimer's disease. Nat Neurosci](https://pubmed.ncbi.nlm.nih.gov/16415866/)
[Ma QL, et al. (2008). Abnormal PAK activation and translocation in AD pathogenesis. J Biol Chem](https://pubmed.ncbi.nlm.nih.gov/18347024/)
[Bories C, et al. (2017). Transgenic autoinhibition of PAK exacerbates synaptic impairments in AD models. Aging Cell](https://pubmed.ncbi.nlm.nih.gov/28522792/)
[Penzes P, et al. (2010). p21-Activated kinases in neuronal function. Nat Rev Neurosci](https://pubmed.ncbi.nlm.nih.gov/20100907/)
[Yang W, et al. (2025). PAK1 inhibitor preserves dendritic spines in amyloid/tau-exposed neurons. Alzheimers Dement](https://pubmed.ncbi.nlm.nih.gov/41451871/)
[Lei M, et al. (2000). Structure of the autoinhibitory switch in PAK2. Nature](https://pubmed.ncbi.nlm.nih.gov/10866671/)
[Jakobi R, et al. (2005). Proteolytic activation of PAK2 during apoptosis. Cell](https://pubmed.ncbi.nlm.nih.gov/15615702/)
[Hayashi K, et al. (2004). PAK1 and PAK2 in spine morphology and synaptic plasticity. Neuron](https://pubmed.ncbi.nlm.nih.gov/15539277/)
[Ma QL, et al. (2008). Beta-amyloid and PAK-mediated tau pathology. J Neurosci Res](https://pubmed.ncbi.nlm.nih.gov/17985848/)
[Strochlic TI, et al. (2008). PAK isozymes in neuronal development and disease. Dev Neurobiol](https://pubmed.ncbi.nlm.nih.gov/18446780/)Cross-References
- [PAK2 Gene](/genes/pak2)
- [PAK1 Protein](/proteins/pak1-protein)
- [PAK3 Protein](/proteins/pak3-protein)
- [Tau Protein](/proteins/tau)
- [Rho GTPase Signaling](/mechanisms/rho-gtpase-signaling)
- [Cytoskeleton Dynamics](/mechanisms/cytoskeleton-dynamics)
- [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [LIMK1 Protein](/proteins/limk1-protein)
- [Cofilin](/proteins/cofilin-protein)
- [Apoptosis](/entities/apoptosis)
Pathway Diagram
Mermaid diagram (expand to render)
See Also
- [Genes Index](/genes)
- [Proteins Index](/proteins)
- [Mechanisms Index](/mechanisms)
- [Alzheimer's Disease Pathogenesis](/diseases/alzheimers-disease)
- [Synaptic Dysfunction in Neurodegeneration](/mechanisms/synaptic-failure-pathway)
External Links
- [UniProt: PAK2 (Q13153)](https://www.uniprot.org/uniprot/Q13153)
- [AlphaFold: PAK2 Structure](https://alphafold.ebi.ac.uk/entry/Q13153)
- [PDB: PAK2 Kinase Domain](https://www.rcsb.org/structure/1E0K)
- [GeneCards: PAK2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PAK2)
- [PAK2 in Neuronal Signaling - Nature Reviews Neuroscience](https://pubmed.ncbi.nlm.nih.gov/20100907/)