Serine/threonine-protein kinase PAK 1

PAK1 (serine/threonine-protein kinase 1) is a cytoplasmic signaling kinase that regulates intracellular pathways downstream of integrins and receptor tyrosine kinases. It plays critical roles in cytoskeleton dynamics, cell migration, proliferation, and apoptosis through phosphorylation of effectors including MAP kinases, tubulin chaperones, and cofilin regulators (UniProt: Q13153). In neurons, PAK1 is particularly important for dendritic spine formation, GABAergic synaptic transmission, and neuromuscular junction development.

PAK1 is associated with an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, macrocephaly, seizures, and speech delay (IDDMSSD; UniProt: Q13153). The protein's roles in actin cytoskeleton organization and synaptic plasticity suggest mechanistic links to developmental neurobiology.

In Alzheimer's disease, PAK1 is significantly down-regulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.32 across multiple subcellular fractions detected by TMT-labeled proteomics (Chaparral AD proteomics). This reduction may reflect diminished cytoskeletal dynamics and synaptic integrity characteristic of AD pathology.