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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 ELISA Kits) 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.
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.
The effect of PAK1 modulation on tumorigenesis, and on resistance to treatment with 5-fluorouracil (5-FU), was measured by sphere formation in vitro and by growth of xenografted tumors in vivo. The results show that PAK1 activity correlated with the expression of CSC markers and the CD44 (show CD44 ELISA Kits) isoform profile, and with tumor growth both in vitro and in vivo.
this study shows that PAK1 may be a potential tumor marker and therapeutic target of prostate cancer
Our results from clinical samples also suggest that Threonine 209 phosphorylation by Pak1 could be a potential therapeutic target and of great clinical relevance with implications for Runx3 (show RUNX3 ELISA Kits) inactivation in cancer cells where Runx3 (show RUNX3 ELISA Kits) is known to be oncogenic. The findings presented in this study provide evidence of Runx3 (show RUNX3 ELISA Kits)-Threonine 209 phosphorylation as a molecular switch in dictating the tissue-specific dualistic functions
Abnormalities in the PAK1 and PAK3 mRNA levels as well as their altered coexpression patterns were observed in the postmortem brain of subjects with depression. Dysregulated PAK1/PAK3 dependent signaling may be a key factor responsible for volumetric abnormalities observed in the hippocampus and in the prefrontal cortex in depression resulting in altered connectivity of these regions.
Short-term treatment of nascent melanoma tumors with PAK inhibitors that block RhoJ (show RHOJ ELISA Kits) signaling halts the growth of BRAF (show BRAF ELISA Kits) mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via a BAD-dependent mechanism
these data strongly support a critical interplay between prolactin (show PRL ELISA Kits) and estrogen via PAK1 and suggest that ligand-independent activation of ERalpha (show ESR1 ELISA Kits) through prolactin (show PRL ELISA Kits)/PAK1 may impart resistance to anti-estrogen therapies.
Given the central role of p21-Activated kinase 1 (PAK1) in vital signaling pathways, studies suggest that clinical development of PAK1 inhibitors will require careful investigation of their safety and efficacy.
These findings suggest that small-molecule inhibitors of Pak1 may have a therapeutic role in the ~25% of ovarian cancers characterized by PAK1 gene amplification.
autocrine VEGF (show VEGFA ELISA Kits) and IL-8 (show IL8 ELISA Kits) promoted endothelial cell migration via the Src (show SRC ELISA Kits)/Vav2 (show VAV2 ELISA Kits)/Rac1/PAK1 signaling pathway.
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 ELISA Kits) as redundant regulators of myoblast differentiation in vitro and in vivo and as components of the promyogenic Ncad (show CDH2 ELISA Kits)/Cdo (show CDO1 ELISA Kits)/Cdc42 (show CDC42 ELISA Kits) 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.
Further investigations identified Pak1-ERM as a downstream signaling cascade upon Rac1 activation in the luminal epithelium necessary for uterine receptivity...Rac1 via P38 MAPK (show MAPK14 ELISA Kits) signaling ensures timely epithelial apoptotic death at postimplantation.
Nischarin (show NISCH ELISA Kits) inhibits neurite outgrowth by blocking PAK1 activation in neurons.
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 ELISA Kits) signaling to regulate tissue polarity and gene expression.
only PAK-1 functions in the GIT/PIX (show ARHGEF7 ELISA Kits)/PAK pathway independently of RAC (show AKT1 ELISA Kits)/CDC42 (show CDC42 ELISA Kits) GTPases.
Data show that combined loss of ROCK and PAK, or ROCK and MRCK (show CDC42BPA ELISA Kits), completely prevented embryonic elongation, but a constitutively active form of MLC-4 could only rescue a lack of MRCK (show CDC42BPA ELISA Kits).
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