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These results implicate a novel role for PAK4 within the PI3K pathway via interaction with p85alpha. Thus, PAK4 could be an essential player in PDAC progression representing an interesting therapeutic opportunity.
This review will discuss the emerging data highlighting the prominence of PAK4 in Pancreatic distal adenocarcinoma(PDAC) and its potential role for transforming patient management.
this series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity
X-ray crystallography reveals that in addition to the canonical PAK4 CDC42/RAC interactive binding (CRIB) domain binding to CDC42 there are unexpected contacts involving the PAK4 kinase C-lobe, CDC42, and the PAK4 polybasic region.
High PAK4 expression is associated with glioma.
These results indicate that miR485 acts as a tumour suppressor in Glioblastoma (GBM) by, at least partially, directly targeting PAK4 and regulating the AKT and ERK signalling pathways. Thus, miR485 may be a potential target for the treatment of patients with GBM.
Study reports the overexpression of PAK4 in neuroblastoma cells and, that PF-3758309, a potent PAK4 inhibitor, inhibits cell proliferation and survival in neuroblastoma cells via inhibition of the MEK/ERK pathway. These results suggest a role of PAK4 in neuroblastoma development.
Methylation at cg14010619 may modify PAK4 activity, which has been implicated in cisplatin resistance in malignant cell lines
PAK4 downregulated the level of p21 and enhanced the activity of Akt as well. And we conclude that PAK4 acts as a regulator of cell cycle progression of vascular smooth muscle cells by mediating Akt signaling and controlling p21 levels, which further modulate intimal hyperplasia and vascular smooth muscle cells proliferation
Findings revealed a novel function of PAK4 in thyroid stimulating hormone-induced papillary thyroid cancer progression.
The present study demonstrates that miR-145 plays an important role in inhibiting cell migration by directly targeting PAK4, and identifies miR-145-PAK4-LIMK1-cofilin as a novel regulatory pathway that contributed to colorectal cancer metastasis.
These findings revealed a novel glucose metabolism-related mechanism of PAK4 in promoting colon cancer cell growth, suggesting that PAK4 and/or G6PD blockage might be a potential therapeutic strategy for colon cancer.
PAK4 (but not PAK1) mediates invadopodia maturation during melanoma invasion likely via inhibition of PDZ-RhoGEF.
these results indicate that PAK4 confers CDDP resistance via the activation of MEK/ERK and PI3K/Akt pathways. PAK4 and PI3K/Akt pathways can reciprocally activate each other.
PAK4 activity was markedly decreased in postmortem brain tissue from Parkinson's disease (PD) patients and in rodent models of PD. Expression of constitutively active PAK4(S445N/S474E) (caPAK4) protected DA neurons in both the 6-hydroxydopamine and alpha-synuclein rat models of PD and preserved motor function.
Our results indicate that PAK4 plays an important role in the potentiation of insulin secretion by fatty acids downstream of GPR40.
PAK4 downregulation decreased PPARgamma-mediated Nox1 expression and suppressed EMT in IR-treated glioma cells.
miR-1271/Zic2/PAK4 axis plays an important role in hepatocellular carcinoma progression.
findings suggest that PAK4-activated PI3K/AKT signaling is both kinase-dependent and -independent, which contributes to breast cancer progression
Functional role and therapeutic targeting of PAK4 in multiple myeloma has been presented.
pak4 is dispensable in zebrafish.
Zebrafish pak4 is required for primitive myeloid cell development.
PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. They serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK4 interacts specifically with the GTP-bound form of Cdc42Hs and weakly activates the JNK family of MAP kinases. PAK4 is a mediator of filopodia formation and may play a role in the reorganization of the actin cytoskeleton. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
, p21(CDKN1A)-activated kinase 4
, p21-activated kinase 4
, protein kinase related to S. cerevisiae STE20, effector for Cdc42Hs
, serine/threonine-protein kinase PAK 4
, p21 (CDKN1A)-activated kinase 4
, p21 protein (Cdc42/Rac)-activated kinase 4