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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 (zeige CDC42 Proteine) 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.
PAK1 expression, evaluated by immunohistochemistry, was positively correlated with pERK (zeige EIF2AK3 Proteine) and beta-catenin (zeige CTNNB1 Proteine) expression in lung tumors. Patients with high-PAK1, high-pERK (zeige EIF2AK3 Proteine), and high-nuclear beta-catenin (zeige CTNNB1 Proteine) tumors more frequently showed an unfavorable response to cisplatin-based chemotherapy when compared to their counterparts.
PKC-zeta (zeige PRKCZ Proteine) may be responsible for the abnormal growth, proliferation, and migration of metastatic LOVO colon cancer cells via PKC-zeta (zeige PRKCZ Proteine)/Rac1/Pak1/beta-Catenin (zeige CTNNB1 Proteine) pathway.
High expression of PAK1 is associated with invasion of gastric cancer.
Molecular modelling studies of PAK1 with its major interacting partners RHOA (zeige RHOA Proteine) and STAT3 (zeige STAT3 Proteine) revealed potential network gene elements in breast invasive carcinoma.
miR4855p reverses EMT (zeige ITK Proteine) 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 (zeige PAK2 Proteine) directly promotes cell invasion by facilitating invadopodia turnover via the Rac1/PAK1/Cortactin (zeige CTTN Proteine) 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 (zeige EGFR Proteine)-mutant cells as well as in EGFR (zeige EGFR Proteine)-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.
Depletion of active PAK1 up-regulates the immune system of APC (zeige APC Proteine)(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 (zeige PARP1 Proteine) 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 (zeige PAK2 Proteine) as redundant regulators of myoblast differentiation in vitro and in vivo and as components of the promyogenic Ncad (zeige CDH2 Proteine)/Cdo (zeige CDO1 Proteine)/Cdc42 (zeige CDC42 Proteine) 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.
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 (zeige WNT2 Proteine) signaling to regulate tissue polarity and gene expression.
only PAK-1 functions in the GIT/PIX (zeige ARHGEF7 Proteine)/PAK pathway independently of RAC (zeige AKT1 Proteine)/CDC42 (zeige CDC42 Proteine) GTPases.
Data show that combined loss of ROCK and PAK, or ROCK and MRCK (zeige CDC42BPA Proteine), completely prevented embryonic elongation, but a constitutively active form of MLC-4 could only rescue a lack of MRCK (zeige CDC42BPA Proteine).
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