title: The Drosophila IKK-related kinase (Ik2) and Spindle-F proteins are part of a complex that regulates cytoskeleton organization during oogenesis.
abstract: BACKGROUND
  IkappaB kinases (IKKs) regulate the activity of Rel/NF-kappaB transcription factors by targeting their inhibitory partner proteins, IkappaBs, for degradation. The Drosophila genome encodes two members of the IKK family. Whereas the first is a kinase essential for activation of the NF-kappaB pathway, the latter does not act as IkappaB kinase. Instead, recent findings indicate that Ik2 regulates F-actin assembly by mediating the function of nonapoptotic caspases via degradation of DIAP1. Also, it has been suggested that ik2 regulates interactions between the minus ends of the microtubules and the actin-rich cortex in the oocyte. Since spn-F mutants display oocyte defects similar to those of ik2 mutant, we decided to investigate whether Spn-F could be a direct regulatory target of Ik2.
  
  
  RESULTS
  We found that Ik2 binds physically to Spn-F, biomolecular interaction analysis of Spn-F and Ik2 demonstrating that both proteins bind directly and form a complex. We showed that Ik2 phosphorylates Spn-F and demonstrated that this phosphorylation does not lead to Spn-F degradation. Ik2 is localized to the anterior ring of the oocyte and to punctate structures in the nurse cells together with Spn-F protein, and both proteins are mutually required for their localization.
  
  
  CONCLUSIONS
  We conclude that Ik2 and Spn-F form a complex, which regulates cytoskeleton organization during Drosophila oogenesis and in which Spn-F is the direct regulatory target for Ik2. Interestingly, Ik2 in this complex does not function as a typical IKK in that it does not direct SpnF for degradation following phosphorylation.
authors.affiliation: Department of Life Science, National Institute for Biotechnology in Negev, Ben-Gurion University, Beer-Sheva, 84105 Israel. bardik@bgu.ac.il
authors.forename: Dikla
authors.initials: D
authors.lastname: Dubin-Bar
authors.forename: Amir
authors.initials: A
authors.lastname: Bitan
authors.forename: Anna
authors.initials: A
authors.lastname: Bakhrat
authors.forename: Rotem
authors.initials: R
authors.lastname: Kaiden-Hasson
authors.forename: Sharon
authors.initials: S
authors.lastname: Etzion
authors.forename: Boaz
authors.initials: B
authors.lastname: Shaanan
authors.forename: Uri
authors.initials: U
authors.lastname: Abdu
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000648:ultrastructure; D004330:Drosophila / Q000378:metabolism / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051550:I-kappa B Kinase / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D009866:Oogenesis; D010766:Phosphorylation
chemical_list: D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; C510862:Spn-F protein, Drosophila; D051550:I-kappa B Kinase; C510861:IKKepsilon protein, Drosophila
references.citation: Development. 2006 Apr;133(8):1477-84
references.pmid: 16540510
references.citation: Genes Dev. 2001 Sep 15;15(18):2321-42
references.pmid: 11562344
references.citation: Cell. 2006 Aug 11;126(3):583-96
references.pmid: 16887178
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):233-8
references.pmid: 14679297
references.citation: Science. 1997 Oct 31;278(5339):860-6
references.pmid: 9346484
references.citation: Protein Expr Purif. 1999 Feb;15(1):34-9
references.pmid: 10024467
references.citation: Genes Dev. 2001 Jan 1;15(1):104-10
references.pmid: 11156609
references.citation: Cell. 1997 Oct 17;91(2):243-52
references.pmid: 9346241
references.citation: Science. 2003 Dec 5;302(5651):1727-36
references.pmid: 14605208
references.citation: Nat Immunol. 2003 May;4(5):491-6
references.pmid: 12692549
references.citation: Biochim Biophys Acta. 2001;1471(2):M57-62
references.pmid: 11342184
references.citation: Development. 2006 Apr;133(8):1467-75
references.pmid: 16540511
references.citation: Anal Biochem. 2004 Feb 15;325(2):301-7
references.pmid: 14751265
references.citation: Nature. 1997 Aug 7;388(6642):548-54
references.pmid: 9252186
references.citation: Science. 1982 Oct 22;218(4570):341-7
references.pmid: 6289435
references.citation: Science. 2003 May 16;300(5622):1148-51
references.pmid: 12702806
references.citation: Cell. 2002 Apr;109 Suppl:S81-96
references.pmid: 11983155
references.citation: Microbiol Rev. 1995 Mar;59(1):94-123
references.pmid: 7708014
references.citation: Curr Opin Chem Biol. 2001 Oct;5(5):572-7
references.pmid: 11578932
references.citation: Genetics. 1992 Jul;131(3):643-53
references.pmid: 1628809
references.citation: J Mol Biol. 2002 Mar 22;317(2):309-23
references.pmid: 11902845
references.citation: Curr Biol. 1998 Feb 12;8(4):243-6
references.pmid: 9501989
references.citation: Curr Biol. 2006 Aug 8;16(15):1531-7
references.pmid: 16887350
references.citation: Genes Dev. 2000 Oct 1;14(19):2461-71
references.pmid: 11018014
references.citation: Anal Biochem. 2006 Nov 15;358(2):281-8
references.pmid: 16962556