The p21-activated kinases (PAK1), PAK2, and PAK3 are members of the PAK group I and share high sequence identity and common biochemical properties. PAK3 is specifically implicated in neuronal plasticity and also regulates cell cycle progression, neuronal migration, and apoptosis. Loss of function of PAK3 is responsible for X-linked non-syndromic mental retardation whereas gain of PAK3 function is associated with cancer. To understand the functional specificities of PAK3, we analyzed the structure of PAK3 gene products. We report here the characterization of a new alternatively spliced exon called c located upstream of the previously identified exon b. Exon b is detected in all tetrapods and not in fish, exon c is only present in mammals. Mammalian PAK3 genes encode four splice variants and the corresponding proteins were detected with specific antibodies in brain extracts. All PAK3 transcripts are specifically expressed in brain and in particular in neurons. The presence of the exons b and c renders the kinase constitutively active and decreases interaction with GTPases. The expression of the new splice variants in COS7 cells alters cell morphology and modifies the structure of focal adhesions. We propose that the appearance of...Continue Reading
A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases.
Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes.
A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1.
Modulation of kinase activity and oncogenic properties by alternative splicing reveals a novel regulatory mechanism for B-Raf.
Sustained activation of the mitogen-activated protein kinase pathway. A mechanism underlying receptor tyrosine kinase specificity for matrix metalloproteinase-9 induction and cell migration.
A new constitutively active brain PAK3 isoform displays modified specificities toward Rac and Cdc42 GTPases.
X-linked mild non-syndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3
Altered cortical synaptic morphology and impaired memory consolidation in forebrain- specific dominant-negative PAK transgenic mice
GEFT, a Rho family guanine nucleotide exchange factor, regulates neurite outgrowth and dendritic spine formation.
Abnormal long-lasting synaptic plasticity and cognition in mice lacking the mental retardation gene Pak3
A novel splice variant of interleukin-1 receptor (IL-1R)-associated kinase 1 plays a negative regulatory role in Toll/IL-1R-induced inflammatory signaling
Central nervous system functions of PAK protein family: from spine morphogenesis to mental retardation
The p21-activated kinase 3 implicated in mental retardation regulates spine morphogenesis through a Cdc42-dependent pathway
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function
p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its interaction with the Nck2/Grb4 protein adaptor.
The p21-activated kinase PAK3 forms heterodimers with PAK1 in brain implementing trans-regulation of PAK3 activity.
P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation
Accelerated evolution of PAK3- and PIM1-like kinase gene families in the zebra finch, Taeniopygia guttata
Functional diversity of human protein kinase splice variants marks significant expansion of human kinome
The 3q29 microdeletion syndrome: report of three new unrelated patients and in silico "RNA binding" analysis of the 3q29 region
Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice
Lethality of PAK3 and SGK2 shRNAs to human papillomavirus positive cervical cancer cells is independent of PAK3 and SGK2 knockdown
Lithium Sensitive ORAI1 Expression, Store Operated Ca2+ Entry and Suicidal Death of Neurons in Chorea-Acanthocytosis.
MicroRNA-24 alleviates isoflurane-induced neurotoxicity in rat hippocampus via attenuation of oxidative stress.
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis