The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

Pak1  -  p21 protein (Cdc42/Rac)-activated kinase 1

Mus musculus

Synonyms: AW045634, Alpha-PAK, CDC42/RAC effector kinase PAK-A, PAK-1, Paka, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of Pak1

  • These findings reveal a novel role for the Pak1-ER pathway in promoting hyperplasia in mammary epithelium [1].
  • Finally, we found that consistent with a role in breast tumor progression, Pak1 expression and its nuclear accumulation was increased progressively during the transition from ductal hyperplasia to ductal carcinoma in situ to adenocarcinoma in widely used multistep polyoma-middle T-antigen transgenic mice [2].
  • Emerging data suggest that p21-activated kinase 1 (Pak1), a downstream signaling molecule of the small GTPases, growth factors, and lipid signaling, is upregulated or hyperactivated in human breast cancer [2].
  • Our results showed that in a transgenic mouse model, overexpression of catalytically active Pak1 leads to the development of malignant mammary tumors and to a variety of other breast lesions, including focal solid nodules, ductal hyperplasia, and mini-intraductal neoplasm and adenoma [2].
  • Outgrowth of neurites from NIE-115 neuroblastoma cells is prevented on repulsive substrates through the action of PAK [3].
 

High impact information on Pak1

 

Chemical compound and disease context of Pak1

 

Biological context of Pak1

 

Anatomical context of Pak1

 

Associations of Pak1 with chemical compounds

 

Regulatory relationships of Pak1

  • We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2 [17].
  • PURPOSE: The major aim of this study was to determine whether Src family kinases are required for both Ras-induced PAK activation and malignant transformation [18].
  • PAK is essential for RAS-induced upregulation of cyclin D1 during the G1 to S transition [19].
  • This co-activation appeared necessary to reach a full stimulation of Rac as well as PAK activation and actin polymerization and was blocked by a G-protein betagamma subunits scavenger peptide [20].
 

Other interactions of Pak1

  • The Rac2 mutants V36A, F37A, and N39A all bind to both Pak1 and p67(phox), yet are unable to rescue superoxide production and chemotaxis when expressed in Rac2-/- PMN [21].
  • These defects were associated with deficiencies of PAK1, GSK3beta, myosin light chain, and FAK phosphorylation [22].
  • We have identified a specific phosphorylation site on mammalian Pak1, T212, which is targeted by the neuronal p35/Cdk5 kinase [12].
  • Recently, overexpression of Xenopus Pak5 was shown to enhance microtubule stabilization, and it was shown that mammalian Pak1 may inhibit a microtubule-destabilizing protein, Op18/Stathmin [12].
  • The cellular mechanism of ExoS GAP activity included an inactivation of Rac1 function, as determined in p21-activated kinase 1-glutathione S-transferase (GST) pull-down assays [23].
 

Analytical, diagnostic and therapeutic context of Pak1

  • Western blot detection of the phosphorylated forms of PAK-1 (Thr423) and Raf-1 (Ser338) confirmed activation of these kinases in permissive cells after MV infection or gamma interferon treatment, but the activated forms of both kinases were greatly reduced or absent in restrictive 3T3 cells [24].
  • Two murine monoclonal antibodies (MoAbs) Pak-1 and Pak-2 were established by immunizing Balb/c mice with human pancreatic adenocarcinoma xenografts, previously established in mice [8].

References

  1. P21-activated kinase-1 phosphorylates and transactivates estrogen receptor-alpha and promotes hyperplasia in mammary epithelium. Wang, R.A., Mazumdar, A., Vadlamudi, R.K., Kumar, R. EMBO J. (2002) [Pubmed]
  2. PAK1 hyperactivation is sufficient for mammary gland tumor formation. Wang, R.A., Zhang, H., Balasenthil, S., Medina, D., Kumar, R. Oncogene (2006) [Pubmed]
  3. Outgrowth of neurites from NIE-115 neuroblastoma cells is prevented on repulsive substrates through the action of PAK. Marler, K.J., Kozma, R., Ahmed, S., Dong, J.M., Hall, C., Lim, L. Mol. Cell. Biol. (2005) [Pubmed]
  4. Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1. Kim, H.W., Yang, P., Qyang, Y., Lai, H., Du, H., Henkel, J.S., Kumar, K., Bao, S., Liu, M., Marcus, S. Mol. Cell (2001) [Pubmed]
  5. Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase. Howe, A.K., Juliano, R.L. Nat. Cell Biol. (2000) [Pubmed]
  6. Altered focal adhesion regulation correlates with cardiomyopathy in mice expressing constitutively active rac1. Sussman, M.A., Welch, S., Walker, A., Klevitsky, R., Hewett, T.E., Price, R.L., Schaefer, E., Yager, K. J. Clin. Invest. (2000) [Pubmed]
  7. Essential functions of p21-activated kinase 1 in morphogenesis and differentiation of mammary glands. Wang, R.A., Vadlamudi, R.K., Bagheri-Yarmand, R., Beuvink, I., Hynes, N.E., Kumar, R. J. Cell Biol. (2003) [Pubmed]
  8. Human pancreatic adenocarcinoma-associated antigens defined by novel murine monoclonal antibodies Pak-1 and Pak-2. Makisumi, K., Takahashi, K., Takako, S., Sonoda, S. Gastroenterol. Jpn. (1990) [Pubmed]
  9. Signal therapy of human pancreatic cancer and NF1-deficient breast cancer xenograft in mice by a combination of PP1 and GL-2003, anti-PAK1 drugs (Tyr-kinase inhibitors). Hirokawa, Y., Levitzki, A., Lessene, G., Baell, J., Xiao, Y., Zhu, H., Maruta, H. Cancer Lett. (2007) [Pubmed]
  10. Cloning, central nervous system expression and chromosomal mapping of the mouse PAK-1 and PAK-3 genes. Burbelo, P.D., Kozak, C.A., Finegold, A.A., Hall, A., Pirone, D.M. Gene (1999) [Pubmed]
  11. Opposing roles for akt1 and akt2 in rac/pak signaling and cell migration. Zhou, G.L., Tucker, D.F., Bae, S.S., Bhatheja, K., Birnbaum, M.J., Field, J. J. Biol. Chem. (2006) [Pubmed]
  12. Pak1 phosphorylation on t212 affects microtubules in cells undergoing mitosis. Banerjee, M., Worth, D., Prowse, D.M., Nikolic, M. Curr. Biol. (2002) [Pubmed]
  13. Regulation of macropinocytosis by p21-activated kinase-1. Dharmawardhane, S., Schürmann, A., Sells, M.A., Chernoff, J., Schmid, S.L., Bokoch, G.M. Mol. Biol. Cell (2000) [Pubmed]
  14. Insulin and insulin-like growth factor-1 promote mast cell survival via activation of the phosphatidylinositol-3-kinase pathway. Lessmann, E., Grochowy, G., Weingarten, L., Giesemann, T., Aktories, K., Leitges, M., Krystal, G., Huber, M. Exp. Hematol. (2006) [Pubmed]
  15. Targeted disruption of the gene for the PAK5 kinase in mice. Li, X., Minden, A. Mol. Cell. Biol. (2003) [Pubmed]
  16. Activation of Rac and Cdc42 by integrins mediates cell spreading. Price, L.S., Leng, J., Schwartz, M.A., Bokoch, G.M. Mol. Biol. Cell (1998) [Pubmed]
  17. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. Kissil, J.L., Johnson, K.C., Eckman, M.S., Jacks, T. J. Biol. Chem. (2002) [Pubmed]
  18. An anti-Ras cancer potential of PP1, an inhibitor specific for Src family kinases: in vitro and in vivo studies. He, H., Hirokawa, Y., Levitzki, A., Maruta, H. Cancer journal (Sudbury, Mass.) (2000) [Pubmed]
  19. PAK is essential for RAS-induced upregulation of cyclin D1 during the G1 to S transition. Nheu, T., He, H., Hirokawa, Y., Walker, F., Wood, J., Maruta, H. Cell Cycle (2004) [Pubmed]
  20. A differential role of the platelet ADP receptors P2Y1 and P2Y12 in Rac activation. Soulet, C., Hechler, B., Gratacap, M.P., Plantavid, M., Offermanns, S., Gachet, C., Payrastre, B. J. Thromb. Haemost. (2005) [Pubmed]
  21. Rac2 regulates neutrophil chemotaxis, superoxide production, and myeloid colony formation through multiple distinct effector pathways. Carstanjen, D., Yamauchi, A., Koornneef, A., Zang, H., Filippi, M.D., Harris, C., Towe, J., Atkinson, S., Zheng, Y., Dinauer, M.C., Williams, D.A. J. Immunol. (2005) [Pubmed]
  22. Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic Fibroblasts. Yang, L., Wang, L., Zheng, Y. Mol. Biol. Cell (2006) [Pubmed]
  23. Characterization of Pseudomonas aeruginosa exoenzyme S as a bifunctional enzyme in J774A.1 macrophages. Rocha, C.L., Coburn, J., Rucks, E.A., Olson, J.C. Infect. Immun. (2003) [Pubmed]
  24. Role of the serine-threonine kinase PAK-1 in myxoma virus replication. Johnston, J.B., Barrett, J.W., Chang, W., Chung, C.S., Zeng, W., Masters, J., Mann, M., Wang, F., Cao, J., McFadden, G. J. Virol. (2003) [Pubmed]
 
WikiGenes - Universities