Báo cáo khoa học: Serine-arginine protein kinases: a small protein kinase family with a large

REVIEW ARTICLE

Serine-arginine protein kinases: a small protein kinase

family with a large cellular presence

Thomas Giannakouros1

, Eleni Nikolakaki1

, Ilias Mylonis2 and Eleni Georgatsou2

1 Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Greece

2 Laboratory of Biochemistry, Department of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

History of the discovery of the

serine-arginine protein kinase

(SPRK) family

The first serine-arginine (SR) protein kinase to be puri￾fied and characterized was named SRPK1, for SR-pro￾tein-specific kinase 1 [1,2]. It was isolated during a

search for the activity that phosphorylates SR splicing

factors (also named SR proteins) during mitosis.

SRPK1 was shown to phosphorylate SR proteins in a

cell-cycle regulated manner, to affect SR protein locali￾zation and to inhibit splicing when added in large

quantities to a cell-free splicing assay [1,2]. The

SRPK1 cDNA was cloned, revealing that the Schizo￾saccharomyces pombe SRPK1 orthologue, Dsk1, had

already been cloned and partially characterized as a

kinase with cell cycle-dependent phosphorylation and

subcellular localization [3]. The SRPK1 and Dsk1

nucleotide sequencing identified a domain interrupting

the kinase catalytic site into two structural entities,

Keywords

LBR; metabolic signalling; nuclear envelope;

p53; PGC-1; protamine; spermatogenesis;

splicing; SR protein; SRPK

Correspondence

E. Georgatsou, Laboratory of Biochemistry,

Department of Medicine, School of Health

Sciences, University of Thessaly, Biopolis,

41110 Larissa, Greece

Fax: +30 2410 685545

Tel: +30 2410 685581

E-mail: [email protected]

(Received 7 July 2010, accepted 26 October

2010)

doi:10.1111/j.1742-4658.2010.07987.x

Serine-arginine protein kinases (SPRKs) constitute a relatively novel

subfamily of serine-threonine kinases that specifically phosphorylate serine

residues residing in serine-arginine ⁄ arginine-serine dipeptide motifs. Fifteen

years of research subsequent to the purification and cloning of human

SRPK1 as a SR splicing factor-phosphorylating protein have lead to the

accumulation of information on the function and regulation of the different

members of this family, as well as on the genomic organization of SRPK

genes in several organisms. Originally considered to be devoted to constitu￾tive and alternative mRNA splicing, SRPKs are now known to expand

their influence to additional steps of mRNA maturation, as well as to other

cellular activities, such as chromatin reorganization in somatic and sperm

cells, cell cycle and p53 regulation, and metabolic signalling. Similarly,

SRPKs were considered to be constitutively active kinases, although several

modes of regulation of their function have been demonstrated, implying an

elaborate cellular control of their activity. Finally, SRPK gene sequence

information from bioinformatics data reveals that SRPK gene homologs

exist either in single or multiple copies in every single eukaryotic organism

tested, emphasizing the importance of SRPK protein function for cellular

life.

Abbreviations

CDK, cyclin dependent kinase; Clk, CDK-like kinase; CK2, casein kinase 2; FOXO1, forkhead box protein O1; HBV, hepatitis B virus;

HP1, heterochromatin protein 1; Hsp, heat shock protein; LBR, lamin B receptor; NRF-1, nuclear respiratory factor-1; PGC-1, peroxisome

proliferator activated receptor c coactivator-1; RS, arginine-serine; SAFB, scaffold attachment factor B; SR, serine-arginine;

SRPK, serine-arginine protein kinase.

570 FEBS Journal 278 (2011) 570–586 ª 2011 The Authors Journal compilation ª 2011 FEBS