title: Structural determinants of LL5beta subcellular localisation and association with filamin C.
abstract: PI3K signalling pathways link cell surface receptors to the control of several intracellular functions including cell growth, survival and movement. Filamins are important regulators of cortical actin structure and function. LL5beta is a filamin binding protein that is an effector of the PI3K signalling pathway. We define an N-terminal region of LL5beta that is responsible for binding to the C-terminus of filamins. Under conditions of very low PI3K activity, we show that this region, together with an additional domain of the protein, is responsible for localising the complex to punctate structures that are also decorated by L-FILIP (a protein previously characterised to bind filamin and accelerate its destruction). Under conditions of significant PI3K activity, PtdIns(3,4,5)P(3) binding to the C-terminal PH domain in LL5beta prevents localisation to these structures. These observations start to define the basis for PI3K regulation of filamin through LL5beta.
authors.affiliation: Inositide Laboratory, The Babraham Institute, Cambridge, UK.
authors.forename: Varuni
authors.initials: V
authors.lastname: Paranavitane
authors.forename: Len R
authors.initials: LR
authors.lastname: Stephens
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Hawkins
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003285:Contractile Proteins / Q000737:chemistry / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D064448:Filamins; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000199:Actins; D002352:Carrier Proteins; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D064448:Filamins; D008840:Microfilament Proteins; D050505:Mutant Proteins; D020033:Protein Isoforms; D010768:Phosphoserine