REVIEW ARTICLE
Serine-arginine protein kinases: a small protein kinase
family with a large cellular presence
Thomas Giannakouros
1
, Eleni Nikolakaki
1
, Ilias Mylonis
2
and Eleni Georgatsou
2
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

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
hence called ‘the spacer domain’, which is characteris-
tic of the SR protein kinase family [3,4]. Subsequently,
Dsk1 was also shown to be a SR protein kinase phos-
phorylating and regulating the function of SR proteins
[5–7].
In 1998, the cloning of SRPK2 was reported almost
simultaneously in mouse (together with mSRPK1) [8]
and man [9]. SRPK2 was found to be a SR-specific
protein kinase highly homologous to SRPK1. It is
structurally differentiated from SRPK1 by a proline-
rich tract at its N-terminus and an acidic region in its
spacer domain. However, none of these elements had
been related to a particular SRPK2-specific function
until recently, when a study showed that sequences
residing in the acidic domain of SRPK2 specifically
interact with the pro-apoptotic arginine-serine (RS)
domain-containing protein acinus [10]. Moreover, the
mRNA of SRPK2 was shown to have a different
and more limited tissue distribution than SRPK1

corresponding to an intron at its N-terminal region,
was reported in 2001 [16]. Interestingly, this domain is
rich in proline residues reminiscent of the proline-rich
SRPK2-specific track. Additionally, the SRPK1a
N-terminus was found to interact with the nuclear
matrix protein scaffold attachment factor (SAFB) B1,
and it was subsequently shown that SAFB proteins are
inhibitors of SRPK1 and SRPK1a activity, function-
ally differentiating between the two kinases and further
implicating SRPKs in subnuclear organization and
chromatin regulation [17].
Mouse SRPK3 was discovered in 2005, having been
identified in a screen for target genes of the transcrip-
tion factor myocyte enhancer factor 2 [18]. SRPK3 is
expressed in a tissue-specific fashion in the heart and
skeletal muscle and is required for normal muscle
growth and homeostasis because Srpk3-null mice suffer
from centronuclear myopathy [18]. It has not been
confirmed, however, whether SR kinase activity is
required for these phenotypes and, if so, what sub-
strates are affected. The existence of the orthologue of
mSRPK3 in humans has been postulated in an analysis
of human chromosomal DNA methylation, although
no studies are available for its expression or function.
However, the cDNA of the porcine SRPK3 has been
cloned and shown to have a very limited and tissue
specific expression in muscular tissue [19].
Although Drosophila harbors several SRPK homo-
logs, only two very recent studies refer to Srpk79D (as
named by both groups), which is considered to be a

sequences of the SRPK gene products.
The first intriguing observation is that the SRPK gene
copy number of an organism does not appear to directly
relate to its evolutionary scale. For example, there
exist fungi with one, two or even up to nine SRPK
genes [S. cerevisiae and S. pombe with one gene (Sky1
and Dsk1, respectively); Candida albicans with two
(QSAA48 and QS9Q27); Aspergilus niger with nine
(A2QAE4, A2QB94, A2QC46, A5AB23, A2QWQ2,
A2QX01, A2QX98, A2R2M0 and A2RSV1)]; plants
with three genes (Ricinus communis; B9SRL4, B9S6V7
and B9SNS8); and insects with two (Culex quinquefasci-
atus; BOWGI3 and BOWRV4) or three genes [Drosoph-
ila melanogaster; CG8174, CG8565 and CG11489
(CG9085)], whereas mammals (rat, mouse, human, etc.)
have three genes. Additionally, as we have experienced
from our own research and as m entioned in the two s tudies
concerning Srpk79D in Drosophila melanogaster [20,21],
there is no prominent one-to-one correspondence
between the sequences of SRPK genes of evolutionary
remote species. The emerging image is reminiscent of
independent SRPK gene duplications that have taken
place at several time points during evolution in different
species. Accordingly, it is suggested that the SRPK
genes are subjected to an evolutionary drive that
demands multiple SRPK gene copies in almost each new
emerging species. One may observe evidence of the
errors of the evolutionary ‘trial and error’ process oper-
ating through new SRPK genes: pseudogenes exist for
both SRPK1 and SRPK2 in the human genome and

Function of the SRPKs
As already noted, SRPKs phosphorylate their
substrates at serine residues located in regions rich in
arginine ⁄ serine dipeptides, known as RS domains. The
definition of a ‘typical’ RS domain is somewhat arbi-
trary and SRPKs have been shown to be able to phos-
phorylate scattered RS dipeptides if they conform to
certain limitations [26–29]. The specificity of these
enzymes is remarkable because mutations of Ser to
Thr or Arg to Lys in the RS domain completely abro-
gate phosphorylation [2,26].
In the list of the RS domain-containing proteins, the
SR proteins prevail, either as the originally identified
‘classical’ SR proteins invariably containing an RNA
recognition motif or as ‘SR-like’ or ‘SR-related’ pro-
teins also containing RNA binding domains (RNA
recognition motif or other). Most of the SR splicing
factors have been experimentally shown to be SRPK
substrates in vitro and in vivo and it is to be expected
that every SR protein could potentially be a SRPK
substrate under particular cellular conditions. Yet a
recent study suggests that the human genome encodes
for more than 100 RS domain-containing proteins [30],
indicating that SRPKs may regulate diverse cellular
functions through phosphorylation of many of these
potential substrates. Below, we review the SRPK
impact on mRNA maturation and discuss the regula-
tory paradigms that have been characterized to a
reasonable extent, including the replacement of hist-
ones by the arginine-rich protamines during spermio-

also relatively recently, Akt kinases have been shown
to affect splicing by targeting RS domains [36]. Third,
the specific functions of the various SRPKs discov-
ered in different organisms are just beginning to be
addressed.
As already mentioned, concomitant with its purifica-
tion, SRPK1 was shown to inhibit splicing in vitro
when present in large quantities and to disassemble
nuclear speckles when added in permeabilized cells [1].
This and other in vitro experiments have implicated
SRPKs in the phosphorylation of SR splicing factors
and the regulation of splicing [2,9,37], although the
first study to definitively attribute a role of a SRPK on
SR protein function in vivo was carried out by Yeakley
et al. [12], which showed that when the unique SRPK
of S. cerevisiae (Sky1) is deleted, the interaction of SR
proteins is prevented, and they are incapable of trans-
locating into the nucleus. Importantly, that study,
which used mammalian splicing factors, showed for
the first time that SRPK-mediated phosphorylation
plays an important role in SR protein nuclear import
and that not all SR splicing factors are affected identi-
cally. Sequential studies with Sky1 and its SR-like pro-
tein substrate Nlp3p (which transports mRNAs out of
the nucleus) have shown that Nlp3p needs to be phos-
phorylated to release the mRNA and be re-imported
into the nucleus [13,38]. In humans, shuttling splicing
factors such as SF2 ⁄ ASF are phosphorylated in the
cytoplasm by SRPK1 (Fig. 1) and are subsequently
Fig. 1. SRPK regulation and function in mRNA maturation. During interphase, SRPKs are sequestered in the cytoplasm via their spacer

is involved in 5¢ splice selection [43], whereas SRPK2
was shown to be required for the formation of the
U4 ⁄ U6-U5 tri-snRNP, which is involved in 3¢ splice site
selection [44]. Similarly, using siRNA, Hayes et al. [45]
have confirmed the role of SRPK1 in phosphorylating
SR proteins in vivo and have connected the endogenous
down-regulation of SRPK1 expression with alternative
splicing of a particular transcript. Finally, Zhong et al.
[46] clearly showed that when SR protein kinases enter
the nucleus (in this case under a stress signal), phos-
phorylation of SR proteins is increased, verifying the
nuclear action of SRPKs on SR splicing factors.
Accordingly, a study by Jiang et al. [47] showed that
when SRPK2 is phosphorylated by Akt in neuronal
cells, it enters the nucleus and is able to phosphorylate
the nonshuttling SR splicing factor SC35.
As previously noted, SR proteins are implicated in a
much broader spectrum of activities that accompany
the life of an mRNA, in addition to the splicing pro-
cess. To function in mRNA export, SR proteins need
to be underphosphorylated (Fig. 1). On the other
hand, SF2 ⁄ ASF does not have to leave the nucleus to
exert its positive effect on mRNA nonsense mediated
decay [48]. An intact RS domain is required for this
particular function, yet the impact of its phosphoryla-
tion state has not been addressed. In addition,
SF2 ⁄ ASF has been recently shown to be a transla-
tional activator of capped mRNAs in the cytoplasm
[49]; however, no report on its state of phosphoryla-
tion was included in that study. The participation of

potential pharmaceutical targets for the control of viral
infection. Hence, a small molecule, isonicotinamide
compound, which is a relatively selective inhibitor of
SRPK1 and 2 (SPRIN340), was found to impair Sind-
bis virus propagation in cultured cells, although it is
only variably effective on HIV-1 propagation [55].
Interest in SRPKs as pharmaceutical targets also
emerged from the observation that SRPKs show
increased expression in tumors of pancreas, breast and
colon [45,56], as well as in acute T-cell leukemia
induced by human T-cell leukemia virus-1 [57].
Accordingly, cell lines derived from pancreatic, breast
and colonic tumors, when disrupted for the SRPK1
gene, display diminished cell proliferation, increased
apoptotic potential and augmented sensitivity to the
common chemotherapeutics gemcitabine and cisplatine.
Evidence has been provided that the results observed
are effected through the splicing machinery [45]. An
inverse correlation has been documented, however,
between the expression of SRPK1 and cisplatin sensi-
tivity in yeast and in cells of germline origin, where
down-regulation of SRPK1 confers resistance to cis-
platin [58,59]. These tissue-specific findings again point
out the intricate and fine-tuned cellular networks regu-
lated by SRPK activity.
Serine-arginine protein kinases T. Giannakouros et al.
574 FEBS Journal 278 (2011) 570–586 ª 2011 The Authors Journal compilation ª 2011 FEBS
SRPKs and spermiogenesis
SRPK1, SRPK1a and SRPK2 are predominantly
expressed in testis [9,15,16]. Because of the numerous

exchange, the nucleosomal-type chromatin is trans-
formed into a smooth fiber and compacted into a
volume approximately 5% of that of a somatic cell
nucleus [63,64]. P1 protamine is the main member of
the family and is conserved in all vertebrates, whereas
P2 protamine has been described only in some species,
including man, stallion, hamster and mouse [63].
The deposition of protamines on sperm chromatin
and the subsequent chromatin condensation are largely
controlled by phosphorylation-dephosphorylation
events. Protamines are highly phosphorylated shortly
after their synthesis and before binding to DNA [65].
Phosphorylation of P2 protamine has been shown to
be essential because deletion of the calmodulin-depen-
dent protein kinase Camk4, which phosphorylates P2
protamine, impairs the deposition of P2 protamine on
sperm chromatin, resulting in defective spermiogenesis
and male sterility [66]. Phosphorylation of P1 prot-
amine by SRPK1 is required for the temporal associa-
tion of P1 protamine with lamin B receptor (LBR), an
inner nuclear membrane protein that also possesses a
stretch of RS dipeptides at its nucleoplasmic NH
2
-
terminal domain [67]. It is well known that RS
domains mediate protein–protein interactions in a
phosphorylation-dependent manner [68], assuming that
only one of the two RS domains is phosphorylated.
Phosphorylation of the P1 protamine molecules in the
cytoplasm on their way to the nucleus together with a

respectively, are known to be responsible for their
translocation into the nucleus [71,72]. Consistent with
this hypothesis, it has been suggested that phosphory-
lation of the RS domain of the splicing factor
ASF ⁄ SF2 by SRPK1 results in a conformational
change that facilitates its interaction with the nuclear
transport receptor transportin-SR2 (an importin-b
family protein), thereby mediating the shuttling of this
SR protein into the nucleus through the nuclear pore
complex [41]. In such a case, phosphorylation of P1
protamine by cytoplasmic SRPK1 may also promote
its interaction with an as yet unknown importin family
member, thereby facilitating its translocation into the
nucleus. The release of P1 protamine from importin
may be mediated through its binding to LBR at the
nuclear periphery.
Finally, SRPKs may have additional roles in sper-
matogenesis that need to be further characterized. For
T. Giannakouros et al. Serine-arginine protein kinases
FEBS Journal 278 (2011) 570–586 ª 2011 The Authors Journal compilation ª 2011 FEBS 575
example, SRPK1 was reported to mediate the uptake
of polyamines through an as yet unidentified signaling
pathway [73].
SRPKs, cell cycle progression and chromatin
reorganization
SRPKs have been characterized as cell cycle regulated
kinases [1,3]. This characterization was mainly based
on the finding that SRPK1, as well as its fission yeast
homolog, Dsk1, can translocate into the nucleus at the
end of the G2 phase [3,4]. In addition, SRPK1 activity,

the arrays of nucleosomes to the nuclear periphery. It
is well known that, during mitosis, the nuclear enve-
lope breaks down and chromosomes dissociate from
the inner nuclear membrane. Already at prophase,
binding of the membranous structures to chromosomes
is weakened. The RS domain of LBR is phosphoryla-
ted at the beginning of mitosis by nuclear-translocated
SRPK1 and potentially by Akt and Clk kinases that
may also target RS domains [26,36]. Furthermore, the
central mitotic kinase, cdk1, phosphorylates LBR at
Ser71 [80], which is located just upstream of the RS
repeats. It is therefore possible that these combinato-
rial phosphorylation events may result in chromosome
dissociation. This idea is consistent with a previous
study reporting that phosphorylation of LBR by mito-
tic extracts impairs chromatin association [81].
Fig. 2. A model illustrating the interactions between the NH
2
-terminal nucleoplasmic domain of LBR and P1 protamine. At the beginning of
spermiogenesis, the RS domain of LBR is unphosphorylated, allowing its association with phosphorylated protamine 1. LBR may act as a
docking site for the replacement of transition proteins (TP) by P1 protamine in certain chromatin layers that come close to the nuclear
periphery. Enzymes trapped in the inner nuclear membrane (INM) may also further modify the P1 protamine molecules, thereby facilitating
their deposition on sperm chromatin. The detachment of P1 protamine from the nuclear envelope and its tight binding to DNA is proposed
to occur through its dephosphorylation, whereas, at the same time, a similar dephosphorylation event may trigger the dissociation of TP
from sperm chromatin.
Serine-arginine protein kinases T. Giannakouros et al.
576 FEBS Journal 278 (2011) 570–586 ª 2011 The Authors Journal compilation ª 2011 FEBS
Regulation of chromatin reorganization during
G2 ⁄ M phase progression
Another mode of action of SRPK1 related to its

[84], and HP1 proteins are well-known constituents of
‘silent’ chromatin, the regulated nuclear translocation
of SRPKs may contribute to the re-positioning and
‘unwinding’ of specific genomic loci, thus leading to
their transcriptional activation.
Regulation of cyclin transcription
SRPK2 has been implicated in the transcriptional
regulation of two members of the cyclin family. In
hematopoietic cells, SRPK2 was reported to enhance
cyclin A1 transcription [10], whereas, in neurons, it
was shown to trigger cell cycle progression and induce
apoptosis through regulation of cyclin D1 [47].
Cyclin A1 is a member of mammalian A-type cyclins
and is mainly expressed in male germ cells, being
essential for the passage of spermatocytes into meiosis
I [85]. In addition to male germ cells, elevated levels of
cyclin A1 expression have been detected in several leu-
kemic cell lines as well as in hematopoietic stem cells
and primitive precursors [86]. Up-regulation of cyclin
A1 by SRPK2 is accomplished through phosphoryla-
tion of the protein acinus that contains several RS
domains and its subsequent redistribution from nuclear
Fig. 3. Modulation of chromatin condensation at the beginning of mitosis by SR protein kinases. The combined phosphorylation of the RS
domain of LBR by nuclear translocated SRPK1 and the central mitotic kinase cdk1 (and potentially by Clk and Akt kinases) results in chromo-
some dissociation from the inner nuclear membrane. A concomitant combined phosphorylation event [i.e. phosphorylation of Ser10 of H3
by aurora B and phosphorylation of SR proteins ASF ⁄ SF2 and SRp20 (SR) by nuclear translocated SRPK1, and potentially by Clk and Akt
kinases] results in HP1 release from mitotic chromatin, further facilitating chromatin condensation.
T. Giannakouros et al. Serine-arginine protein kinases
FEBS Journal 278 (2011) 570–586 ª 2011 The Authors Journal compilation ª 2011 FEBS 577
speckles to the cytoplasm [10]. Acinus was originally

apoptosis through regulation of nuclear cyclin D1 [47].
According to Jang et al. [47], up-regulation of cyclin
D1 in this system is not mediated through acinus phos-
phorylation but rather through inactivation of p53.
More specifically, it has been proposed that SRPK2
phosphorylates and activates SC35 and, thus, it may
inactivate p53 by blocking its phosphorylation at
Ser15 [47,90]. Interestingly, it has been also reported
that SC35 affects transcriptional elongation in a gene-
specific manner [91]. Thus, activation of SC35 may
lead to down-regulation of specific genes, including
p53. Because p53 represses cyclin D1 expression [92],
down-regulation of p53 may also result in cyclin D1
up-regulation.
In this respect, it should be noted that SRPKs have
been proposed to act as modifiers of the p53 pathway
in Drosophila (Patent WO ⁄ 2002 ⁄ 099427: SRPKs as
modifiers of the p53 pathway). More specifically, a
genetic screen identified that a SRPK mutation
enhanced cell death, as induced by the expression of
p53 in the Drosophila wing. Because Drosophila con-
tains more than one Srpk gene, it remains unclear
whether the regulation of p53 activity is exerted by a
specific SRPK (e.g. the SRPK2 homolog) and, more
importantly, whether this regulation is accomplished
solely through SC35.
SRPKs and metabolic signaling
The PGC-1 family of coactivators mediates various
environmental signals, thus regulating several meta-
bolic pathways in a tissue-specific manner [93]. Most

scriptional activity. It was previously shown that
SRPK1 can phosphorylate in vitro the RS domain of
PGC-1a [79], although a similar phosphorylation event
has not yet been shown to occur in vivo. We anticipate
that this type of phosphorylation may also take place
in vivo and not only by SRPK1, but also by other
members of the SRPK family, to an extent propor-
tional to the expression levels of SRPKs in liver.
Another important issue is the response to insulin.
Akt2 is an insulin-responsive kinase, whereas it was
shown to phosphorylate Clk2 at Thr343, leading to an
increase of Clk2 protein stability and therefore activity
[98]. Clk2 was therefore suggested to function as
an insulin-induced gluconeogenic repressor. Yet Akt
Serine-arginine protein kinases T. Giannakouros et al.
578 FEBS Journal 278 (2011) 570–586 ª 2011 The Authors Journal compilation ª 2011 FEBS
kinases can also phosphorylate SRPK2 at Thr492 and
mediate its nuclear translocation [47], thus making
SRPK2 an insulin-responsive kinase as well. It is still
unknown whether insulin has any effect on SRPK1
and ⁄ or on SRPK1a, either directly through phosphor-
ylation by Akt kinases or through another indirect sig-
nalling mechanism. In this respect, it should be noted
that SRPK1a contains two LXXLL motifs [16] that
are assumed to facilitate the interaction of different
proteins with nuclear receptors. All these phosphoryla-
tion events may act in a complementary fashion
(Fig. 4A), thus constituting a fine-tuning mechanism
that modulates the interaction of PGC-1a with various
transcription factors and allows the expression of

and further strengthens the hypothesis that SRPKs
may be actively involved in the phosphorylation of
PGC-1a. Fogal et al. [100], extending previous obser-
vations [101], reported that p32 protein plays a decisive
role in maintaining mitochondrial oxidative phosphor-
ylation. Knocking down p32 expression in human can-
cer cells resulted in a reduced expression of oxidative
phosphorylation-related polypeptides and shifted the
cell metabolism from oxidative phosphorylation to gly-
colysis. p32 is an ‘all-around’ cellular protein found in
the nucleus, cytoplasm, mitochondria and cell surface
with essentially unknown physiological role(s) [102].
Yet p32 was reported to bind the RS domains of both
ASF ⁄ SF2 and LBR and inhibit the phosphorylation of
these molecules by SRPKs [67,103,104]. Even though it
remains to be proven, we speculate that p32 protein
drives PGC-1a activity toward specific gene sets
involved in oxidative phosphorylation by obstructing
its interaction with FOXO1, thus allowing the avai-
lable molecules to interact with NRF-1 (Fig. 4B).
Regulation of the SRPK family
members
SRPKs have been considered to be constitutively
active kinases because the expression of SRPK family
members in bacteria, which lack the post-translational
modification machinery of eukaryotic cells, has shown
that they are able to efficiently phosphorylate their
substrates [26,29,105]. Furthermore, co-expression of
SRPK1 and its substrate SF2 ⁄ ASF in Escherichia coli
results in the phosphorylation and splicing activity of

been shown to be mediated by their association with
specific members of molecular chaperones (Fig. 1).
Thus, direct interaction of SRPK1 with cochaperones
Aha1 and heat shock protein Hsp40 mediates the for-
mation of a complex with the Hsp70 ⁄ Hsp90 machinery
[46]. Furthermore, SRPK2 directly associates with the
-b and -e isoforms of 14-3-3 family of proteins in an
Akt phosphorylation-depended manner in the cyto-
plasm of neuronal cells [47].
The interaction of SRPK1 with the molecular chap-
erones could be modulated by signal(s) resulting in the
release and subsequent translocation of the kinase to
the nucleus. One option is that SRPKs may be post-
translationally modified in response to signaling. In
this respect, a previous study indicated that SRPK1 is
phosphorylated and partially activated by casein
kinase 2 (CK2) [109]. However, it remains to be deter-
mined whether CK2 has any effect on the nuclear
translocation of the kinase. Furthermore, Akt was pro-
posed to mediate the nuclear translocation of SRPK2
by phosphorylating it at Thr492, whereas 14-3-3 mole-
cules were shown to interact with Akt-phosphorylated
SRPK2 and inhibit its nuclear translocation [47]. Of
note, the major CK2 phosphorylation site (
SDDD,
Ser51 in human SRPK1) is conserved among SRPK
family members, whereas the Akt site (HDRSR
TVS,
Thr492 in human SRPK2) is not, and probably repre-
sents a SRPK2-specific mode of regulation. A second

be modified in vivo by MS in kinome-wide phospho-
proteomics studies in HeLa cells [111–113]. These
reports also indicate the existence of additional
phosphorylation sites on SRPK molecules (http://
www.phosphosite.org/homeAction.do; keywords
‘SRPK1’ and ‘SRPK2’), suggesting that there is more
than one unidentified signal, which could affect either
their activity or shuttling through the modulation of
their interaction with other proteins.
Another aspect of the modulation SRPK activity
involves transient interaction with nonshuttling protein
complexes. It was recently shown that both SRPK1
and SRPK1a could directly interact with SAFB1 and
SAFB2, albeit with different affinities. This association
does not depend on the spacer domain, as was shown
for other protein complexes of SRPK1, but rather on
the N-terminal and core kinase domains. Interaction
with SAFB molecules impaired the catalytic activity of
SRPK1 ⁄ 1a, whereas the nuclear subfraction of the
kinases, which was found to be associated with the
nuclear matrix via SAFB proteins, was inactive [17].
Given that SAFB proteins are also sequestrated in
stress-induced subnuclear bodies, along with splicing
factors and RNA molecules in response to stress
[114,115], it is intriguing to consider that their interac-
tion with SRPK1 ⁄ 1a and subsequent inactivation of
the kinases could provide an additional mechanism of
controlling SRPK activity when the cell needs to react
promptly to a variety of signals.
Conclusions

nology and the Greek Ministry of Education.
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