Pak4

Summary

Gene Symbol: Pak4
Description: p21 (RAC1) activated kinase 4
Alias: 5730488L07Rik, AW555722, mKIAA1142, serine/threonine-protein kinase PAK 4, PAK-4, p21 protein (Cdc42/Rac)-activated kinase 4, p21-activated kinase 4
Species: mouse
Products:     Pak4

Top Publications

  1. Liu Y, Xiao H, Tian Y, Nekrasova T, Hao X, Lee H, et al. The pak4 protein kinase plays a key role in cell survival and tumorigenesis in athymic mice. Mol Cancer Res. 2008;6:1215-24 pubmed publisher
    b>Pak4 is a member of the B group of p21-activated (Pak) kinases, originally identified as an effector protein for Cdc42. Although Pak4 is expressed at low levels in most adult tissues, it is highly overexpressed in tumor cell lines...
  2. Dolan B, Duron S, Campbell D, Vollrath B, Shankaranarayana Rao B, Ko H, et al. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci U S A. 2013;110:5671-6 pubmed publisher
    ..Finally, a single administration of FRAX486 is sufficient to rescue all of these phenotypes in adult Fmr1 KO mice, demonstrating the potential for rapid, postdiagnostic therapy in adults with FXS. ..
  3. Bright M, Frankel G. PAK4 phosphorylates myosin regulatory light chain and contributes to Fc? receptor-mediated phagocytosis. Int J Biochem Cell Biol. 2011;43:1776-81 pubmed publisher
    ..Taken together, these data indicate that p21-activated kinase 4 regulates regulatory myosin light chain phosphorylation and myosin contractility during Fc?R-mediated phagocytosis. ..
  4. Liu Y, Chen N, Cui X, Zheng X, Deng L, Price S, et al. The protein kinase Pak4 disrupts mammary acinar architecture and promotes mammary tumorigenesis. Oncogene. 2010;29:5883-94 pubmed publisher
    The Pak4 serine/threonine kinase is highly expressed in many cancer cell lines and human tumors. Although several studies have addressed the role for Pak4 in transformation of fibroblasts, most human cancers are epithelial in origin...
  5. Ha U, Lim J, Kim H, Wu W, Jin S, Xu H, et al. MKP1 regulates the induction of MUC5AC mucin by Streptococcus pneumoniae pneumolysin by inhibiting the PAK4-JNK signaling pathway. J Biol Chem. 2008;283:30624-31 pubmed publisher
    ..Here we show that the PAK4-JNK signaling pathway acted as a negative regulator for Streptococcus pneumoniae pneumolysin-induced MUC5AC mucin ..
  6. Nekrasova T, Minden A. PAK4 is required for regulation of the cell-cycle regulatory protein p21, and for control of cell-cycle progression. J Cell Biochem. 2011;112:1795-806 pubmed publisher
    The serine/threonine kinase PAK4 regulates cytoskeletal architecture, and controls cell proliferation and survival...
  7. Zhang E, Ha B, Boggon T. PAK4 crystal structures suggest unusual kinase conformational movements. Biochim Biophys Acta Proteins Proteom. 2018;1866:356-365 pubmed publisher
    ..We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077)...
  8. Pan S, Fei A, Jing L, Zhang X, Gao C. Increased Circulating Endothelial Microparticles Associated with PAK4 Play a Key Role in Ventilation-Induced Lung Injury Process. Biomed Res Int. 2017;2017:4902084 pubmed publisher
    ..VILI inhibited the cytoskeleton-regulating protein of PAK4 and was accompanied by an increased circulating EMP level...
  9. Nekrasova T, Minden A. Role for p21-activated kinase PAK4 in development of the mammalian heart. Transgenic Res. 2012;21:797-811 pubmed publisher
    The serine-threonine kinase PAK4 plays a pivotal role in cell proliferation, survival, and control of the cytoskeleton. Mice that lack Pak4 die in midgestation prior to embryonic day E11 from unidentified causes...

More Information

Publications24

  1. Tian Y, Lei L, Cammarano M, Nekrasova T, Minden A. Essential role for the Pak4 protein kinase in extraembryonic tissue development and vessel formation. Mech Dev. 2009;126:710-20 pubmed publisher
    b>Pak4 is a member of the group B family of Pak serine/threonine kinases, originally identified as an effector protein for the Rho GTPase Cdc42. Pak4 knockout mice are embryonic lethal and do not survive past embryonic day 11.5...
  2. Cammarano M, Nekrasova T, Noel B, Minden A. Pak4 induces premature senescence via a pathway requiring p16INK4/p19ARF and mitogen-activated protein kinase signaling. Mol Cell Biol. 2005;25:9532-42 pubmed
    ..This is most likely a protective function that prevents uncontrolled proliferation. Pak4 is a target for the Rho GTPase Cdc42...
  3. Qu J, Li X, Novitch B, Zheng Y, Kohn M, Xie J, et al. PAK4 kinase is essential for embryonic viability and for proper neuronal development. Mol Cell Biol. 2003;23:7122-33 pubmed
    The serine/threonine kinase PAK4 is a target for the Rho GTPase Cdc42 and has been shown to regulate cell morphology and cytoskeletal organization in mammalian cells...
  4. Michaud E, Culiat C, Klebig M, Barker P, Cain K, Carpenter D, et al. Efficient gene-driven germ-line point mutagenesis of C57BL/6J mice. BMC Genomics. 2005;6:164 pubmed
    ..The ability of ENU to induce mutations that cause various types of changes in proteins will provide additional insights into the functions of mammalian proteins that may not be detectable by knockout mutations. ..
  5. Callow M, Zozulya S, Gishizky M, Jallal B, Smeal T. PAK4 mediates morphological changes through the regulation of GEF-H1. J Cell Sci. 2005;118:1861-72 pubmed
    ..Here we show that p21-activated-kinase 4 (PAK4) mediates morphological changes through its association with the Rho-family guanine nucleotide exchange factor (GEF)..
  6. Barac A, Basile J, Vazquez Prado J, Gao Y, Zheng Y, Gutkind J. Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor. J Biol Chem. 2004;279:6182-9 pubmed
    ..to Rho activation, binds through its C-terminal region to the serine-threonine kinase p21-activated kinase 4 (PAK4), an effector for Cdc42...
  7. Gnad F, Young A, Zhou W, Lyle K, Ong C, Stokes M, et al. Systems-wide analysis of K-Ras, Cdc42, and PAK4 signaling by quantitative phosphoproteomics. Mol Cell Proteomics. 2013;12:2070-80 pubmed publisher
    Although K-Ras, Cdc42, and PAK4 signaling are commonly deregulated in cancer, only a few studies have sought to comprehensively examine the spectrum of phosphorylation-mediated signaling downstream of each of these key signaling nodes...
  8. Yun C, You S, Kim J, Chung J, Han S, Shin E, et al. p21-activated kinase 4 critically regulates melanogenesis via activation of the CREB/MITF and β-catenin/MITF pathways. J Invest Dermatol. 2015;135:1385-1394 pubmed publisher
    p21-activated kinase 4 (PAK4) regulates a wide range of cellular events, including cytoskeletal remodeling, cell growth, and survival...
  9. Li X, Minden A. Targeted disruption of the gene for the PAK5 kinase in mice. Mol Cell Biol. 2003;23:7134-42 pubmed
    ..The phenotypes of the PAK5-null mice are completely different from those of mice null for PAK4, another member of the group B PAK family...
  10. Jin D, Durgan J, Hall A. Functional cross-talk between Cdc42 and two downstream targets, Par6B and PAK4. Biochem J. 2015;467:293-302 pubmed publisher
    ..Two Cdc42 target proteins, the kinase PAK4 [p21 protein (Cdc42/Rac)-activated kinase 4] and the scaffold partitioning defective (Par) 6B, are required to ..
  11. Chintala H, Krupska I, Yan L, LAU L, Grant M, Chaqour B. The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling. Development. 2015;142:2364-74 pubmed publisher
    ..These data highlight novel functions of CCN1 as a naturally optimized molecule, fine-controlling key processes in physiological angiogenesis and safeguarding against aberrant angiogenic responses. ..
  12. Danzer K, Schnack C, Sutcliffe A, Hengerer B, Gillardon F. Functional protein kinase arrays reveal inhibition of p-21-activated kinase 4 by alpha-synuclein oligomers. J Neurochem. 2007;103:2401-7 pubmed
    ..with globular alpha-synuclein oligomers significantly inhibited autophosphorylation of p21-activated kinase (PAK4) compared to treatment with monomeric alpha-synuclein or beta-synuclein...
  13. Lu Y, Pan Z, Devaux Y, Ray P. p21-activated protein kinase 4 (PAK4) interacts with the keratinocyte growth factor receptor and participates in keratinocyte growth factor-mediated inhibition of oxidant-induced cell death. J Biol Chem. 2003;278:10374-80 pubmed
    ..The PAKs are regulated by the Rho-family GTPases Rac and Cdc42. PAK4 is the most divergent member of the PAK family of proteins and may have distinct functions...
  14. Tian Y, Lei L, Minden A. A key role for Pak4 in proliferation and differentiation of neural progenitor cells. Dev Biol. 2011;353:206-16 pubmed publisher
    The Pak4 serine/threonine kinase regulates cytoskeletal organization, and controls cell growth, proliferation, and survival. Deletion of Pak4 in mice results in embryonic lethality prior to embryonic day 11.5...
  15. Choi S, Yeon J, Ryu B, Kim K, Moon S, Lee H, et al. Repositioning Potential of PAK4 to Osteoclastic Bone Resorption. J Bone Miner Res. 2015;30:1494-507 pubmed publisher
    ..Here we investigated the possibility of using the anticancer p21-activated kinase 4 (PAK4)-targeted inhibitor PF-3758309 to treat osteoclast-mediated disorders...