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results represent the first evidence that Pak1 links extracellular signals to the genetic cascade of transcription factors necessary for cranial neural crest specification
These findings expand the role of phosphoinositides in kinase signaling and suggest how altered phosphoinositide metabolism may upregulate Pak1 activity in cancer cells.
The data suggest that EphA4 activation sequesters active Cdc42 (show CDC42 Proteins) and in this way down-regulates cell-cell adhesion.
Pak1 inhibition interferes with the guidance of mesendoderm migration by directional cues residing in the extracellular matrix of the blastocoel roof, and with mesendoderm translocation in the embryo.
The nuclear functions of PAK1 and its role in the regulation of DNA damage repair is reviewed.
PAK1 is upregulated in cutaneous T cell lymphoma. PAK1 silencing induced apoptosis and inhibited cell growth by stimulating the expression of PUMA (show BBC3 Proteins) and p21 (show CDKN1A Proteins).
Results show that JMJD6 (show JMJD6 Proteins) regulates the alternative splicing of PAK1 in melanoma cells.
PAK1 expression, evaluated by immunohistochemistry, was positively correlated with pERK (show EIF2AK3 Proteins) and beta-catenin (show CTNNB1 Proteins) expression in lung tumors. Patients with high-PAK1, high-pERK (show EIF2AK3 Proteins), and high-nuclear beta-catenin (show CTNNB1 Proteins) tumors more frequently showed an unfavorable response to cisplatin-based chemotherapy when compared to their counterparts.
PKC-zeta (show PRKCZ Proteins) may be responsible for the abnormal growth, proliferation, and migration of metastatic LOVO colon cancer cells via PKC-zeta (show PRKCZ Proteins)/Rac1/Pak1/beta-Catenin (show CTNNB1 Proteins) pathway.
High expression of PAK1 is associated with invasion of gastric cancer.
Molecular modelling studies of PAK1 with its major interacting partners RHOA (show RHOA Proteins) and STAT3 (show STAT3 Proteins) revealed potential network gene elements in breast invasive carcinoma.
miR4855p reverses EMT (show ITK Proteins) and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma. This study suggests that PAK1 plays an essential role in the progression of OSCC and it is a potential therapeutic target for OSCC.
Because reduced PAK1 activity impaired FA/BRCA function, inhibition of this kinase in PAK1 amplified and/or overexpressing breast cancer cells represents a plausible strategy for expanding the utility of PARP inhibitors to FA/BRCA-proficient cancers.
Overall, the authors find that p27 (show PAK2 Proteins) directly promotes cell invasion by facilitating invadopodia turnover via the Rac1/PAK1/Cortactin (show CTTN Proteins) pathway.
Serine/threonine-protein kinase (show HIPK2 Proteins) proteins, also known as P21-activated kinase (PAK), and the mechanosensitive factor, Yes-associated protein 1 (YAP-1 (show YAP1 Proteins)) are core mediators of pro-fibrotic integrin beta-1 (show ITGB1 Proteins) signaling.
activated Pak1 regulates chromatin condensation by promoting H3 Ser (show SIGLEC1 Proteins)(10) phosphorylation in oocytes after the resumption of meiotic progression
Depletion of active PAK1 up-regulates the immune system of APC (show APC Proteins)(14/+) mice and suppresses intestinal tumour development. These observations suggest an important role for PAK1 in the immune response to tumours.
Because reduced PAK1 activity impaired FA/BRCA function, inhibition of this kinase in PAK1 amplified and/or overexpressing breast cancer cells represents a plausible strategy for expanding the utility of PARP (show PARP1 Proteins) inhibitors to FA/BRCA-proficient cancers.
Results from our analysis showed that Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA damage via ATR
These results establish a novel signaling process whereby PAK1 upregulates COX-2, reduces anandamide levels and restricts tonic endocannabinoids-mediated processes.
The findings suggest that PAK1 deficiency may underlie an increased diabetic susceptibility. Discovery of ways to remediate glycaemic dysregulation via altering PAK1 or its downstream effectors offers promising opportunities for disease intervention.
present work presents the correlation between DSCAM gene overexpression and a dysregulation of the PAK pathway, resulting in altered morphological parameters of neuronal plasticity in the trisomic cell line, namely decreased number and length of processes
These results identify Pak1 and Pak2 (show PAK2 Proteins) as redundant regulators of myoblast differentiation in vitro and in vivo and as components of the promyogenic Ncad (show CDH2 Proteins)/Cdo (show CDO1 Proteins)/Cdc42 (show CDC42 Proteins) signaling pathway.
PAK-mediated phosphorylation of PKD1 at Ser203 triggers its membrane dissociation and subsequent entry into the nucleus, thereby regulating the phosphorylation of PKD1 nuclear targets, including class IIa histone deacetylases.
FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are most likely conserved from C. elegans to higher organisms.
PAK1 promotes reproduction, whereas it inactivates HSP16.2 gene and shortens lifespan.
Pak-1 interacts with Wnt (show WNT2 Proteins) signaling to regulate tissue polarity and gene expression.
only PAK-1 functions in the GIT/PIX (show ARHGEF7 Proteins)/PAK pathway independently of RAC (show AKT1 Proteins)/CDC42 (show CDC42 Proteins) GTPases.
Data show that combined loss of ROCK and PAK, or ROCK and MRCK (show CDC42BPA Proteins), completely prevented embryonic elongation, but a constitutively active form of MLC-4 could only rescue a lack of MRCK (show CDC42BPA Proteins).
This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
p21 GTPase-associated kinase 1
, p21-activated kinase 1
, p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)
, putative CDKN1A-activated kinase 1
, STE20 homolog, yeast
, p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related)
, serine/threonine-protein kinase PAK 1
, CDC42/RAC effector kinase PAK-A
, activated protein kinase alpha
, p21 (CDKN1A)-activated kinase 1
, protein kinase MUK2