title: Role of the pleckstrin homology domain in intersectin-L Dbl homology domain activation of Cdc42 and signaling.
abstract: Intersectin-long (ITSN-L) contains the invariant Dbl homology (DH) and pleckstrin homology (PH) domain structure characteristic of the majority of Dbl family proteins. This strict domain topography suggests that the PH domain serves an essential, conserved function in the regulation of the intrinsic guanine nucleotide exchange activity of the DH domain. We evaluated the role of the PH domain in regulating the DH domain function of ITSN-L. Surprisingly, we found that the PH domain was dispensable for guanine nucleotide exchange activity on Cdc42 in vitro, yet the PH domain enhanced the ability of the DH domain to activate Cdc42 signaling in vivo. PH domains can interact with phosphoinositide substrates and products of phosphatidylinositol 3-kinase (PI3K). However, PI3K activation did not modulate ITSN-L DH domain function in vivo.
authors.affiliation: Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Pruitt
authors.forename: Antoine E
authors.initials: AE
authors.lastname: Karnoub
authors.forename: A Corinne
authors.initials: AC
authors.lastname: Rakauskas
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Alexei
authors.initials: A
authors.lastname: Kurakin
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kay
authors.forename: John
authors.initials: J
authors.lastname: Sondek
authors.forename: David P
authors.initials: DP
authors.lastname: Siderovski
authors.forename: Channing J
authors.initials: CJ
authors.lastname: Der
mesh_terms: D016475:3T3 Cells; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001798:Blood Proteins; D002352:Carrier Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C115919:intersectin 1; C039077:platelet protein P47; D019869:Phosphatidylinositol 3-Kinases; D020764:cdc42 GTP-Binding Protein