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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 (show CDC42 Proteins)/RAC (show AKT1 Proteins) interactive binding (CRIB (show SCRIB Proteins)) domain binding to CDC42 (show CDC42 Proteins) there are unexpected contacts involving the PAK4 kinase C-lobe, CDC42 (show CDC42 Proteins), 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 (show AKT1 Proteins) and ERK (show EPHB2 Proteins) signalling pathways. Thus, miR485 may be a potential target for the treatment of patients with GBM.
Study reports the overexpression of PAK4 in neuroblastoma (show ARHGEF16 Proteins) cells and, that PF-3758309, a potent PAK4 inhibitor, inhibits cell proliferation and survival in neuroblastoma (show ARHGEF16 Proteins) cells via inhibition of the MEK (show MAP2K1 Proteins)/ERK (show EPHB2 Proteins) pathway. These results suggest a role of PAK4 in neuroblastoma (show ARHGEF16 Proteins) 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 (show CDKN1A Proteins) and enhanced the activity of Akt (show AKT1 Proteins) as well. And we conclude that PAK4 acts as a regulator of cell cycle (show C13orf15 Proteins) progression of vascular smooth muscle cells by mediating Akt (show AKT1 Proteins) signaling and controlling p21 (show CDKN1A Proteins) 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 (show MLXIP Proteins)-145 plays an important role in inhibiting cell migration by directly targeting PAK4, and identifies miR (show MLXIP Proteins)-145-PAK4-LIMK1 (show LIMK1 Proteins)-cofilin (show CFL1 Proteins) as a novel regulatory pathway that contributed to colorectal cancer metastasis.
PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may indicate different mechanisms of regulation.
PAK4 microparticles may have a role in the ventilation-induced lung injury process
These data demonstrate the relevance of PAK4 in osteoclast differentiation and the potential of PAK4 inhibitors for treating osteoclast-related disorders.
PAK4 promotes alpha-MSH/UVB-induced melanogenesis via the CREB (show CREB1 Proteins) and Wnt (show WNT2 Proteins)/beta-catenin (show CTNNB1 Proteins) signaling pathways and suggest that PAK4 may be a potential therapeutic target in pigmentation disorders.
PAK4 phosphorylates Par6B (show PARD6B Proteins) at Ser143 blocking its interaction with Cdc42 (show CDC42 Proteins).
Defined here is the overlap in phosphopeptides regulated by K-Ras (show HRAS Proteins), Cdc42 (show CDC42 Proteins), and PAK4; perturbation of these signaling components affects phosphoproteins associated with microtubule depolymerization, cytoskeletal organization, and the cell cycle.
These results indicate that PAK4 functions, including control of actin dynamics, are necessary for normal development of the heart
p21-activated kinase 4 regulates regulatory myosin light chain phosphorylation and myosin contractility during FcgammaR-mediated phagocytosis.
the transient increase in PAK4 levels at early G1 reduces p21 levels, thereby abrogating the activity of CDK4 (show CDK4 Proteins)/CDK6 (show CDK6 Proteins) kinases, and allowing cells to proceed with the cell cycle in a precisely coordinated way
Conditional Pak4 knockout mice were born normally, but displayed growth retardation and died prematurely. The brains showed a dramatic decrease in proliferation of cortical and striatal neuronal progenitor cells.
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