title: 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.
abstract: Changes in cell morphology are essential in the development of a multicellular organism. The regulation of the cytoskeleton by the Rho subfamily of small GTP-binding proteins is an important determinant of cell shape. The Rho subfamily has been shown to participate in a variety of morphogenetic processes during Drosophila melanogaster development. We describe here a Drosophila homolog, DPAK, of the serine/threonine kinase PAK, a protein which is a target of the Rho subfamily proteins Rac and Cdc42. Rac, Cdc42, and PAK have previously been implicated in signaling by c-Jun amino-terminal kinases. DPAK bound to activated (GTP-bound) Drosophila Rac (DRacA) and Drosophila Cdc42. Similarities in the distributions of DPAK, integrin, and phosphotyrosine suggested an association of DPAK with focal adhesions and Cdc42- and Rac-induced focal adhesion-like focal complexes. DPAK was elevated in the leading edge of epidermal cells, whose morphological changes drive dorsal closure of the embryo. We have previously shown that the accumulation of cytoskeletal elements initiating cell shape changes in these cells could be inhibited by expression of a dominant-negative DRacA transgene. We show that leading-edge epidermal cells flanking segment borders, which express particularly large amounts of DPAK, undergo transient losses of cytoskeletal structures during dorsal closure. 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.
authors.affiliation: Glaxo-IMCB Group, Institute of Molecular and Cell Biology, National University of Singapore.
authors.forename: N
authors.initials: N
authors.lastname: Harden
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: H Y
authors.initials: HY
authors.lastname: Loh
authors.forename: Y M
authors.initials: YM
authors.lastname: Ong
authors.forename: I
authors.initials: I
authors.lastname: Tan
authors.forename: T
authors.initials: T
authors.lastname: Leung
authors.forename: E
authors.initials: E
authors.lastname: Manser
authors.forename: L
authors.initials: L
authors.lastname: Lim
mesh_terms: D000199:Actins / Q000032:analysis / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017931:DNA Primers; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D004817:Epidermis / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D019000:Phosphotyrosine / Q000032:analysis; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins
chemical_list: D000199:Actins; C090145:Cdc42 protein, Drosophila; D017931:DNA Primers; D029721:Drosophila Proteins; D016023:Integrins; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; C099277:Pak protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins