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Gene Review

Pak  -  PAK-kinase

Drosophila melanogaster

Synonyms: CG10295, D-Pak, DPAK, DPak, DPak1, ...
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High impact information on Pak

  • Genetic studies revealed that Dscam, Dock and Pak, a serine/threonine kinase, act together to direct pathfinding of Bolwig's nerve, containing a subclass of sensory axons, to an intermediate target in the embryo [1].
  • We propose that distinct signals transduced via Trio and Dock act combinatorially to activate Pak in spatially restricted domains within the growth cone, thereby controlling the direction of axon extension [2].
  • These data define a signaling pathway from Trio to Rac to Pak that links guidance receptors to the growth cone cytoskeleton [2].
  • Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila [2].
  • Dock and Pak colocalize to R cell axons and growth cones, physically interact, and their loss-of-function phenotypes are indistinguishable [3].

Biological context of Pak

  • The p21 activated kinase (Pak) family of protein kinases are involved in many cellular functions like re-organisation of the cytoskeleton, transcriptional control, cell division, and survival [4].
  • Group I Pak kinase activity in the amnioserosa is required for correct morphogenesis of the epidermis, and may be a component of the signaling known to occur between these two tissues [5].
  • The Drosophila gene mushroom bodies tiny (mbt) encodes a putative p21-activated kinase (PAK), a family of proteins that has been implicated in a multitude of cellular processes including regulation of the cytoskeleton, cell polarisation, control of MAPK signalling cascades and apoptosis [6].
  • Down regulation of the leading edge cytoskeleton may be controlled by the serine/threonine kinase DPAK, a potential Drac1/Dcdc42 effector [7].

Anatomical context of Pak

  • Here, we show that postsynaptic p21-activated kinase (Pak) signaling diverges into two genetically separable pathways at the Drosophila neuromuscular junction [8].

Regulatory relationships of Pak

  • Dock is not necessary for Pak localization but is necessary to restrict Pak signaling to control glutamate receptor abundance [8].
  • A second genetically separable function of Pak kinase signaling controls muscle membrane specialization through the regulation of synaptic Discs-large [8].
  • We propose that DPAK may be regulating the cytoskeleton through its association with focal adhesions and focal complexes and may be participating with DRacA in a c-Jun amino-terminal kinase signaling pathway recently demonstrated to be required for dorsal closure [9].

Other interactions of Pak


  1. Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Schmucker, D., Clemens, J.C., Shu, H., Worby, C.A., Xiao, J., Muda, M., Dixon, J.E., Zipursky, S.L. Cell (2000) [Pubmed]
  2. Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila. Newsome, T.P., Schmidt, S., Dietzl, G., Keleman, K., Asling, B., Debant, A., Dickson, B.J. Cell (2000) [Pubmed]
  3. Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila. Hing, H., Xiao, J., Harden, N., Lim, L., Zipursky, S.L. Cell (1999) [Pubmed]
  4. The Drosophila p21 activated kinase Mbt regulates the actin cytoskeleton and adherens junctions to control photoreceptor cell morphogenesis. Menzel, N., Schneeberger, D., Raabe, T. Mech. Dev. (2007) [Pubmed]
  5. dPak is required for integrity of the leading edge cytoskeleton during Drosophila dorsal closure but does not signal through the JNK cascade. Conder, R., Yu, H., Ricos, M., Hing, H., Chia, W., Lim, L., Harden, N. Dev. Biol. (2004) [Pubmed]
  6. Mbt, a Drosophila PAK protein, combines with Cdc42 to regulate photoreceptor cell morphogenesis. Schneeberger, D., Raabe, T. Development (2003) [Pubmed]
  7. Participation of small GTPases in dorsal closure of the Drosophila embryo: distinct roles for Rho subfamily proteins in epithelial morphogenesis. Harden, N., Ricos, M., Ong, Y.M., Chia, W., Lim, L. J. Cell. Sci. (1999) [Pubmed]
  8. Coordinating structural and functional synapse development: postsynaptic p21-activated kinase independently specifies glutamate receptor abundance and postsynaptic morphology. Albin, S.D., Davis, G.W. J. Neurosci. (2004) [Pubmed]
  9. A Drosophila homolog of the Rac- and Cdc42-activated serine/threonine kinase PAK is a potential focal adhesion and focal complex protein that colocalizes with dynamic actin structures. Harden, N., Lee, J., Loh, H.Y., Ong, Y.M., Tan, I., Leung, T., Manser, E., Lim, L. Mol. Cell. Biol. (1996) [Pubmed]
  10. Isolation of Rho GTPase effector pathways during axon development. Kim, M.D., Kamiyama, D., Kolodziej, P., Hing, H., Chiba, A. Dev. Biol. (2003) [Pubmed]
  11. Genghis Khan (Gek) as a putative effector for Drosophila Cdc42 and regulator of actin polymerization. Luo, L., Lee, T., Tsai, L., Tang, G., Jan, L.Y., Jan, Y.N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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