title: Protein kinase a-dependent phosphorylation of serine 119 in the proto-oncogenic serine/arginine-rich splicing factor 1 modulates its activity as a splicing enhancer protein.
abstract: Serine/arginine-rich splicing factor 1 (SRSF1), previously designated SF2/ASF, belongs to a family of SR proteins that regulate constitutive and alternative splicing. SRSF1 expression is increased in tumors from several tissues and elicits changes in key target genes involved in tumor genesis. Several protein kinases phosphorylate SRSF1, which regulates its localization and function. It is previously reported that protein kinase A (PKA) phosphorylates SRSF1, but the importance of this modification is not well characterized. Here, we show that PKA phosphorylates SRSF1 on serine 119 in vitro. Phosphorylation of SRSF1 on this site enhanced the RNA binding capacity of SRSF1 in vivo and reduced the protein's capacity to activate splicing of the Minx transcript in vitro. We also confirm an interaction between SRSF1 and PKA Cα1 and demonstrate that this interaction is not dependent on serine 119 phosphorylation but requires active PKA Cα1. We conclude that PKA phosphorylation of SRSF1 at serine 119 regulates SFRS1-dependent RNA binding and processing but not its interaction with PKA.
authors.affiliation: Department of Nutrition, University of Oslo, Oslo, Norway.
authors.forename: Anne Kristin
authors.initials: AK
authors.lastname: Aksaas
authors.forename: Sissel
authors.initials: S
authors.lastname: Eikvar
authors.forename: Göran
authors.initials: G
authors.lastname: Akusjärvi
authors.forename: Bjørn S
authors.initials: BS
authors.lastname: Skålhegg
authors.forename: Anne Katrine
authors.initials: AK
authors.lastname: Kvissel