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Gene Review

SRPK1  -  SRSF protein kinase 1

Homo sapiens

Synonyms: SFRS protein kinase 1, SFRSK1, SR-protein-specific kinase 1, Serine/arginine-rich protein-specific kinase 1
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Disease relevance of SRPK1

  • Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein [1].
  • Subsequently, we investigated the role of SRPK1 in cisplatin sensitivity and resistance in human ovarian carcinoma A2780 cells using antisense oligodeoxynucleotides [2].
  • Autologous antibody to SRPK1 was confirmed in the ATL patient using Western blot analysis with plasma, but not detected in asymptomatic HTLV-I carriers or in healthy volunteers [3].

High impact information on SRPK1

  • Our results indicate that SRPK1 may have a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells, and the reorganization of nuclear speckles during mitosis [4].
  • We find that this docking motif restricts phosphorylation of ASF/SF2 by SRPK1 to the N-terminal part of the RS domain - a property essential for its assembly into nuclear speckles [5].
  • Incubation of recombinant caspases with in vitro-translated SRPKs demonstrates that SRPK1 and SRPK2 are in vitro substrates for caspases-8 and -9, respectively [6].
  • SRPK1 is activated early during apoptosis, followed by caspase-mediated proteolytic inactivation at later time points [6].
  • We propose that ICP27 modifies SRPK1 activity resulting in hypophosphorylation of SR proteins impairing their ability to function in spliceosome assembly [7].

Biological context of SRPK1

  • We report here the cloning and characterization of SRPK2, which is highly related to SRPK1 in sequence, kinase activity, and substrate specificity [8].
  • Human SRPK1, which was first identified as a kinase specific for the SR family of splicing factors, is located on chromosome 6p21.2-p21 [9].
  • Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes [10].
  • These results suggest that the docking motif of ASF/SF2 is a key regulatory element for sequential phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its subcellular localization [5].
  • The spacers in mammalian SRPK1 and SRPK2 share little sequence homology, but they function interchangeably in restricting the kinases in the cytoplasm [11].

Anatomical context of SRPK1


Associations of SRPK1 with chemical compounds

  • Coordinately, the disruption of SRPK1 expression resulted in enhanced sensitivity of tumor cells to killing by gemcitabine and/or cisplatin [13].
  • Bleomycin resistance in mammalian cells expressing a genetic suppressor element derived from the SRPK1 gene [14].
  • Using a panel of chromatography media, inhibition by heparin, immunoblot analysis, and phosphopeptide mapping, CK2 was determined to be the major kinase that phosphorylates SRPK1 [15].
  • Synthesis of selective SRPK-1 inhibitors: novel tricyclic quinoxaline derivatives [16].

Physical interactions of SRPK1

  • Based upon a model of SRPK1 bound to a segment encompassing the docking motif and active-site peptide of ASF/SF2, we suggest a mechanism for processive phosphorylation and propose that the atypical resiliency we observed is critical for SRPK1's processive activity [17].

Enzymatic interactions of SRPK1

  • In a search for testis-specific substrates of SRPK1 we found that the enzyme phosphorylates human protamine 1 as well as a cytoplasmic pool of SR proteins present in the testis [12].

Other interactions of SRPK1

  • SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells [8].
  • SRPK1 and LBR protein kinases show identical substrate specificities [18].
  • We also observed vertebrate-specific expansion of the CLK and SRPK kinases (which phosphorylate SR proteins), and the CUG-BP/CELF family of splicing regulators [19].
  • Whereas exposure to OXA in HT29 induced significant changes in expression of many of the genes analyzed, only ATP7A, XPD and SRPK1 gene expression was increased in OXA-treated HTOXAR3 resistant cells [20].
  • This analysis revealed that the gene order from VPS52 to SRPK1 is conserved between human and swine and that comparison with the human sequence identified a rearrangement in the swine genome at the proximal end of VPS52 [21].

Analytical, diagnostic and therapeutic context of SRPK1

  • Using immunohistochemistry, we have localized the expression of a central splicing regulator, serine-arginine protein kinase 1 (SRPK1), to the ductular epithelial cells within human pancreas and have further shown its increased expression in tumors of the pancreas, breast, and colon [13].
  • Randomly selected GCTs (n = 70) and tumors from patients responding to standard chemotherapy (n = 20) generally showed strong SRPK1 staining [22].


  1. Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein. Daub, H., Blencke, S., Habenberger, P., Kurtenbach, A., Dennenmoser, J., Wissing, J., Ullrich, A., Cotten, M. J. Virol. (2002) [Pubmed]
  2. SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and inactivation of its human homologue, SRPK1, induces cisplatin resistance in a human ovarian carcinoma cell line. Schenk, P.W., Boersma, A.W., Brandsma, J.A., den Dulk, H., Burger, H., Stoter, G., Brouwer, J., Nooter, K. Cancer Res. (2001) [Pubmed]
  3. Serological identification of adult T-cell leukaemia-associated antigens. Hishizawa, M., Imada, K., Sakai, T., Ueda, M., Hori, T., Uchiyama, T. Br. J. Haematol. (2005) [Pubmed]
  4. A serine kinase regulates intracellular localization of splicing factors in the cell cycle. Gui, J.F., Lane, W.S., Fu, X.D. Nature (1994) [Pubmed]
  5. Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2. Ngo, J.C., Chakrabarti, S., Ding, J.H., Velazquez-Dones, A., Nolen, B., Aubol, B.E., Adams, J.A., Fu, X.D., Ghosh, G. Mol. Cell (2005) [Pubmed]
  6. Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway. Kamachi, M., Le, T.M., Kim, S.J., Geiger, M.E., Anderson, P., Utz, P.J. J. Exp. Med. (2002) [Pubmed]
  7. ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering SR protein phosphorylation. Sciabica, K.S., Dai, Q.J., Sandri-Goldin, R.M. EMBO J. (2003) [Pubmed]
  8. SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells. Wang, H.Y., Lin, W., Dyck, J.A., Yeakley, J.M., Songyang, Z., Cantley, L.C., Fu, X.D. J. Cell Biol. (1998) [Pubmed]
  9. Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B. Nikolakaki, E., Kohen, R., Hartmann, A.M., Stamm, S., Georgatsou, E., Giannakouros, T. J. Biol. Chem. (2001) [Pubmed]
  10. Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes. Wang, H.Y., Arden, K.C., Bermingham, J.R., Viars, C.S., Lin, W., Boyer, A.D., Fu, X.D. Genomics (1999) [Pubmed]
  11. Regulated cellular partitioning of SR protein-specific kinases in mammalian cells. Ding, J.H., Zhong, X.Y., Hagopian, J.C., Cruz, M.M., Ghosh, G., Feramisco, J., Adams, J.A., Fu, X.D. Mol. Biol. Cell (2006) [Pubmed]
  12. SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1. Papoutsopoulou, S., Nikolakaki, E., Chalepakis, G., Kruft, V., Chevaillier, P., Giannakouros, T. Nucleic Acids Res. (1999) [Pubmed]
  13. Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma. Hayes, G.M., Carrigan, P.E., Beck, A.M., Miller, L.J. Cancer Res. (2006) [Pubmed]
  14. Bleomycin resistance in mammalian cells expressing a genetic suppressor element derived from the SRPK1 gene. Sanz, G., Mir, L., Jacquemin-Sablon, A. Cancer Res. (2002) [Pubmed]
  15. Protein kinase CK2 phosphorylates and activates the SR protein-specific kinase 1. Mylonis, I., Giannakouros, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  16. Synthesis of selective SRPK-1 inhibitors: novel tricyclic quinoxaline derivatives. Székelyhidi, Z., Pató, J., Wáczek, F., Bánhegyi, P., Hegymegi-Barakonyi, B., Erös, D., Mészáros, G., Hollósy, F., Hafenbradl, D., Obert, S., Klebl, B., Kéri, G., Orfi, L. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
  17. SR protein kinase 1 is resilient to inactivation. Ngo, J.C., Gullingsrud, J., Giang, K., Yeh, M.J., Fu, X.D., Adams, J.A., McCammon, J.A., Ghosh, G. Structure (2007) [Pubmed]
  18. SRPK1 and LBR protein kinases show identical substrate specificities. Papoutsopoulou, S., Nikolakaki, E., Giannakouros, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  19. Systematic genome-wide annotation of spliceosomal proteins reveals differential gene family expansion. Barbosa-Morais, N.L., Carmo-Fonseca, M., Aparício, S. Genome Res. (2006) [Pubmed]
  20. Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells. Plasencia, C., Martínez-Balibrea, E., Martinez-Cardús, A., Quinn, D.I., Abad, A., Neamati, N. Int. J. Oncol. (2006) [Pubmed]
  21. Genomic structure and gene order of swine chromosome 7q1.1-->q1.2. Tanaka, M., Suzuki, K., Morozumi, T., Kobayashi, E., Matsumoto, T., Domukai, M., Eguchi-Ogawa, T., Shinkai, H., Awata, T., Uenishi, H. Anim. Genet. (2006) [Pubmed]
  22. Resistance to platinum-containing chemotherapy in testicular germ cell tumors is associated with downregulation of the protein kinase SRPK1. Schenk, P.W., Stoop, H., Bokemeyer, C., Mayer, F., Stoter, G., Oosterhuis, J.W., Wiemer, E., Looijenga, L.H., Nooter, K. Neoplasia (2004) [Pubmed]
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