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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 (zeige CDC42 Proteine)/RAC (zeige AKT1 Proteine) interactive binding (CRIB (zeige SCRIB Proteine)) domain binding to CDC42 (zeige CDC42 Proteine) there are unexpected contacts involving the PAK4 kinase C-lobe, CDC42 (zeige CDC42 Proteine), 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 (zeige AKT1 Proteine) and ERK (zeige EPHB2 Proteine) signalling pathways. Thus, miR485 may be a potential target for the treatment of patients with GBM.
Study reports the overexpression of PAK4 in neuroblastoma (zeige ARHGEF16 Proteine) cells and, that PF-3758309, a potent PAK4 inhibitor, inhibits cell proliferation and survival in neuroblastoma (zeige ARHGEF16 Proteine) cells via inhibition of the MEK (zeige MAP2K1 Proteine)/ERK (zeige EPHB2 Proteine) pathway. These results suggest a role of PAK4 in neuroblastoma (zeige ARHGEF16 Proteine) 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 (zeige CDKN1A Proteine) and enhanced the activity of Akt (zeige AKT1 Proteine) as well. And we conclude that PAK4 acts as a regulator of cell cycle (zeige C13orf15 Proteine) progression of vascular smooth muscle cells by mediating Akt (zeige AKT1 Proteine) signaling and controlling p21 (zeige CDKN1A Proteine) 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 (zeige MLXIP Proteine)-145 plays an important role in inhibiting cell migration by directly targeting PAK4, and identifies miR (zeige MLXIP Proteine)-145-PAK4-LIMK1 (zeige LIMK1 Proteine)-cofilin (zeige CFL1 Proteine) 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 (zeige CREB1 Proteine) and Wnt (zeige WNT2 Proteine)/beta-catenin (zeige CTNNB1 Proteine) signaling pathways and suggest that PAK4 may be a potential therapeutic target in pigmentation disorders.
PAK4 phosphorylates Par6B (zeige PARD6B Proteine) at Ser143 blocking its interaction with Cdc42 (zeige CDC42 Proteine).
Defined here is the overlap in phosphopeptides regulated by K-Ras (zeige HRAS Proteine), Cdc42 (zeige CDC42 Proteine), 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 (zeige CDK4 Proteine)/CDK6 (zeige CDK6 Proteine) 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