title: dPak is required for integrity of the leading edge cytoskeleton during Drosophila dorsal closure but does not signal through the JNK cascade.
abstract: The Pak kinases are effectors for the small GTPases Rac and Cdc42 and are divided into two subfamilies. Group I Paks possess an autoinhibitory domain that can suppress their kinase activity in trans. In Drosophila, two Group I kinases have been identified, dPak and Pak3. Rac and Cdc42 participate in dorsal closure of the embryo, a process in which a hole in the dorsal epidermis is sealed through migration of the epidermal flanks over a tissue called the amnioserosa. Dorsal closure is driven in part by an actomyosin contractile apparatus at the leading edge of the epidermis, and is regulated by a Jun amino terminal kinase (JNK) cascade. Impairment of dPak function using either loss-of-function mutations or expression of a transgene encoding the autoinhibitory domain of dPak led to disruption of the leading edge cytoskeleton and defects in dorsal closure but did not affect the JNK cascade. 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. We conclude that dorsal closure requires Group I Pak function in both the amnioserosa and the epidermis.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada V5A 1S6.
authors.forename: Ryan
authors.initials: R
authors.lastname: Conder
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Michael
authors.initials: M
authors.lastname: Ricos
authors.forename: Huey
authors.initials: H
authors.lastname: Hing
authors.forename: William
authors.initials: W
authors.lastname: Chia
authors.forename: Louis
authors.initials: L
authors.lastname: Lim
authors.forename: Nicholas
authors.initials: N
authors.lastname: Harden
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology* / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010641:Phenotype; D019000:Phosphotyrosine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D019076:Transgenes; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D054462:p21-Activated Kinases; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019000:Phosphotyrosine; C099277:Pak protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein