title: Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.
abstract: The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.
authors.affiliation: Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Polgar
authors.forename: Christina
authors.initials: C
authors.lastname: Leisser
authors.forename: Susanne
authors.initials: S
authors.lastname: Maier
authors.forename: Stephan
authors.initials: S
authors.lastname: Strasser
authors.forename: Beate
authors.initials: B
authors.lastname: Rüger
authors.forename: Markus
authors.initials: M
authors.lastname: Dettke
authors.forename: Maya
authors.initials: M
authors.lastname: Khorchide
authors.forename: Ingrid
authors.initials: I
authors.lastname: Simonitsch
authors.forename: Christa
authors.initials: C
authors.lastname: Cerni
authors.forename: Georg
authors.initials: G
authors.lastname: Krupitza
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002889:Chromosomes, Human, Pair 2; D002895:Chromosomes, Human, Pair 5; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D014178:Translocation, Genetic
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases