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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.
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.
Results show that Pak1 is overexpressed in breast cancer cells and tissues, and found that Pak1 is a hormone responsive gene, whose expression can be modulated by steroid hormones, estrogen (E2) and progesterone (P4). Pak1 promoter analysis showed that PR mediates promoter activity via its binding to PRE present on the Pak1 promoter.
PAK1 confers TKI resistance in EGFR (show EGFR Proteins)-mutant cells as well as in EGFR (show EGFR Proteins)-wild-type cells.
Our findings offer an insight for the new drug development of PAK1 inhibitor. We also provide a possible explanation for the phenomenon that the application of the chlorhexidine in peritoneal lavage inhibited the development of tumor.
To our knowledge, this is the first study illustrating the mechanistic role of Pak1 in causing gemcitabine resistance via multiple signaling crosstalks, and hence Pak1-specific inhibitors will prove to be a better adjuvant with existing chemotherapy modality for pancreatic ductal adenocarcinoma (PDAC)
Studies indicate that PAK1 expression may be a predictive marker of overall survival and disease-specific survival in patients with solid tumors.
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.
the oxidative stress-induced (show SQSTM1 Proteins) down-regulation of PAK1 activity could be involved in the loss of mesencephalic dopaminergic neurons.
the expression of PAK1 is inversely correlated with the level of miR (show MLXIP Proteins)-494 in human breast cancer samples. Furthermore, re-expression of PAK1 partially reverses miR (show MLXIP Proteins)-494-mediated proliferative and clonogenic inhibition as well as migration and invasion suppression in breast cancer cells
Our study revealed that PAK1 may play a crucial role in the progression of OSCC. Studying the role of PAK1 and its substrates is likely to enhance our understanding of oral carcinogenesis and potential therapeutic value of PAKs in oral cancer.
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.
These results implicate PAK1 as a regulator of Pancreatic stellate cells activation, proliferation and apoptosis. Targeting stromal PAK1 could increase therapeutic response and survival of patients with pancreatic cancer.
The authors conclude that PAK1, besides its role in virus entry, also plays a relevant role in vaccinia virus dissemination.
PAK1 contributes to initiation of intestinal carcinogenesis
Pak1 is essential for adaptive physiological exercise-induced cardiac remodelling and support previous evidence that demonstrates Pak1 signalling is important for cardiac growth and survival.
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