TAILIEUCHUNG - Báo cáo khoa học: Major phosphorylation of SF1 on adjacent Ser-Pro motifs enhances interaction with U2AF65

Protein phosphorylation ensures the accurate and controlled expression of the genome, for instance by regulating the activities of pre-mRNA splicing factors. Here we report that splicing factor 1 (SF1), which is involved in an early step of intronic sequence recognition, is highly phosphorylated in mam-malian cells on two serines within an SPSP motif at the junction between its U2AF 65 and RNA binding domains. | ềFEBS Journal Major phosphorylation of SF1 on adjacent Ser-Pro motifs enhances interaction with U2AF65 a IÓ t i o l l anroai 11 M attho A A O ncr n2 loan-PioKro I o ao t 3 AnHró Qnhol1 Plara I lối ol Izonf2 V aiciic Iviai lUcau iviaiuievv u vvei loui I deal iriciic Lc Vdvi HI line uuuei viaia L. Ixieiixup I and Alexandre Maucuer1 1 INSERM U706 UPMC Institut du Fer à Moulin Paris France 2 Department of Biochemistry and Molecular Biology Johns Hopkins University Bloomberg Schoolof Public Health Baltimore MD USA 3 Ecole Polytechnique Laboratoire de Chimie des Mecanismes Reactionnels Palaiseau France Keywords protein phosphorylation RNA splicing SF1 kinase KIS U2AF homology motif Correspondence A. Maucuer INSERM U706 17 rue du Fer a Moulin F-75005 Paris France Fax 33 14587 6132 Tel 33 14587 6139 E-mail maucuer@ Received 14 October 2005 revised 5 December 2005 accepted 6 December 2005 doi Protein phosphorylation ensures the accurate and controlled expression of the genome for instance by regulating the activities of pre-mRNA splicing factors. Here we report that splicing factor 1 SF1 which is involved in an early step of intronic sequence recognition is highly phosphorylated in mammalian cells on two serines within an SPSP motif at the junction between its U2AF65 and RNA binding domains. We show that SF1 interacts in vitro with the protein kinase KIS which possesses a U2AF homology motif UHM domain. The UHM domain of KIS is required for KIS and SF1 to interact and for KIS to efficiently phosphorylate SF1 on the SPSP motif. Importantly SPSP phosphorylation by KIS increases binding of SF1 to U2AF65 and enhances formation of the ternary SF1-U2AF65-RNA complex. These results further suggest that this phosphorylation event has an important role for the function of SF1 and possibly for the structural rearrangements associated with spliceosome assembly and function. The expression of the genome requires the precise and .

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