title: The ratio of SRPK1/SRPK1a regulates erythroid differentiation in K562 leukaemic cells.
abstract: SRPK1, the prototype of the serine/arginine family of kinases, has been implicated in the regulation of multiple cellular processes such as pre-mRNA splicing, chromatin structure, nuclear import and germ cell development. SRPK1a is a much less studied isoform of SRPK1 that contains an extended N-terminal domain and so far has only been detected in human testis. In the present study we show that SRPK1 is the predominant isoform in K562 cells, with the ratio of the two isoforms being critical in determining cell fate. Stable overexpression of SRPK1a induces erythroid differentiation of K562 cells. The induction of globin synthesis was accompanied by a marked decrease in proliferation and a significantly reduced clonogenic potential. Small interfering RNA-mediated down-regulation of SRPK1 in K562 cells results similarly in a decrease in proliferative capacity and induction of globin synthesis. A decreased SRPK1/SRPK1a ratio is also observed upon hemin/DMSO-induced differentiation of K562 cells as well as in normal human erythroid progenitor cells. Mass spectrometric analysis of SRPK1a-associated proteins identified multiple classes of RNA-binding proteins including RNA helicases, heterogeneous nuclear ribonucleoproteins, ribosomal proteins, and mRNA-associated proteins. Several of the SRPK1a-copurifying proteins have been previously identified in ribosomal and pre-ribosomal complexes, thereby suggesting that SRPK1a may play an important role in linking ribosomal assembly and/or function to erythroid differentiation in human leukaemic cells.
authors: Laboratory of Biochemistry, Department of Chemistry, The Aristotle University, 54124, Thessaloniki, Greece.
authors: Ioannis
authors: I
authors: Sanidas
authors: Vassiliki
authors: V
authors: Kotoula
authors: Eleni
authors: E
authors: Ritou
authors: Jasmijn
authors: J
authors: Daans
authors: Christof
authors: C
authors: Lenz
authors: Mario
authors: M
authors: Mairhofer
authors: Makrina
authors: M
authors: Daniilidou
authors: Andrea
authors: A
authors: Kolbus
authors: Volker
authors: V
authors: Kruft
authors: Peter
authors: P
authors: Ponsaerts
authors: Eleni
authors: E
authors: Nikolakaki
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D004912:Erythrocytes / Q000166:cytology*; D006801:Humans; D020014:K562 Cells; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology
chemical_list: D017931:DNA Primers; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases