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

• Pak signaling within this pathway is specified by a required interaction with the adaptor protein Dreadlocks (Dock) [8].
• For two of the three known Pak proteins in Drosophila melanogaster, D-Pak and Mbt, distinct functions during eye development have been established [4].
• Mbt, a Drosophila PAK protein, combines with Cdc42 to regulate photoreceptor cell morphogenesis [6].
• While hyperactivation of Pak itself does not lead to axon outgrowth defects as when Rac1 is constitutively activated, live analysis reveals that it can alter filopodial activity within specific subsets of neurons similar to constitutive activation of Cdc42 [10].
• Whereas the effector for mitogen-activated protein kinase activation appears to be p65PAK, the identity of effector(s) for actin polymerization remains unclear [11].

References