SRPK1

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SRPK1
Protein SRPK1 PDB 1wak.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SRPK1, SFRSK1, SRSF protein kinase 1
External IDs MGI: 106908 HomoloGene: 110962 GeneCards: SRPK1
RNA expression pattern
PBB GE SRPK1 202199 s at fs.png

PBB GE SRPK1 202200 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003137

NM_016795

RefSeq (protein)

NP_003128

NP_058075.2
NP_058075

Location (UCSC) Chr 6: 35.83 – 35.92 Mb Chr 17: 28.59 – 28.62 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Serine/threonine-protein kinase SRPK1 is an enzyme that in humans is encoded by the SRPK1 gene.[3][4][5]

Function[edit]

This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. A second alternatively spliced transcript variant for this gene has been described, but its full length nature has not been determined.[5]

Possible anti-cancer target[edit]

Some cancers are vascular endothelial growth factor (VEGF) dependant (for angiogenesis). SRPK1 activates (phosphorylates) VEGF splicing factor. SRPK1 inhibitors (e.g. 'SPHINX compounds' [6]) are being investigated as treatments for prostate cancer.[7][8]

SRPK1 enables angiogenesis, which is regulated by VEGF, which either initiates or inhibits vessel formation depending on alternative splicing. In human prostate cancer, levels of SRPK1 rose as a cancer becomes more aggressive. In a mouse model three doses per week of drugs designed to inhibit SRPK1 activity inhibitef tumor vasculature and growth.[9]

Interactions[edit]

SRPK1 has been shown to interact with:

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Gui JF, Lane WS, Fu XD (Jul 1994). "A serine kinase regulates intracellular localization of splicing factors in the cell cycle". Nature. 369 (6482): 678–82. doi:10.1038/369678a0. PMID 8208298. 
  4. ^ Wang HY, Arden KC, Bermingham JR, Viars CS, Lin W, Boyer AD, Fu XD (May 1999). "Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes". Genomics. 57 (2): 310–5. doi:10.1006/geno.1999.5770. PMID 10198174. 
  5. ^ a b "Entrez Gene: SRPK1 SFRS protein kinase 1". 
  6. ^ Development of novel anti-angiogenic SRPK1 inhibitors
  7. ^ Molecular breakthrough could halt spread of prostate cancer
  8. ^ "Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer.". Oncogene. 2014. doi:10.1038/onc.2014.360. PMID 25381816. 
  9. ^ Lavars, Nick (November 11, 2014). "Targeting a single molecule may stop prostate cancer in its tracks". www.gizmag.com. Retrieved 2016-04-10. 
  10. ^ a b Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD (Feb 1998). "SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells". J. Cell Biol. 140 (4): 737–50. doi:10.1083/jcb.140.4.737. PMC 2141757Freely accessible. PMID 9472028. 
  11. ^ Lukasiewicz R, Velazquez-Dones A, Huynh N, Hagopian J, Fu XD, Adams J, Ghosh G (Aug 2007). "Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions". J. Biol. Chem. 282 (32): 23036–43. doi:10.1074/jbc.M611305200. PMID 17517895. 
  12. ^ Umehara H, Nishii Y, Morishima M, Kakehi Y, Kioka N, Amachi T, Koizumi J, Hagiwara M, Ueda K (Feb 2003). "Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A". Biochem. Biophys. Res. Commun. 301 (2): 324–9. doi:10.1016/s0006-291x(02)03017-6. PMID 12565863. 
  13. ^ Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR, Hagiwara M (Apr 1999). "The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs)". J. Biol. Chem. 274 (16): 11125–31. doi:10.1074/jbc.274.16.11125. PMID 10196197. 
  14. ^ Kamachi M, Le TM, Kim SJ, Geiger ME, Anderson P, Utz PJ (Nov 2002). "Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway". J. Exp. Med. 196 (9): 1213–25. doi:10.1084/jem.20021167. PMC 2194102Freely accessible. PMID 12417631. 
  15. ^ Varjosalo, Markku; Keskitalo, Salla; Van Drogen, Audrey; Nurkkala, Helka; Vichalkovski, Anton; Aebersold, Ruedi; Gstaiger, Matthias (April 2013). "The Protein Interaction Landscape of the Human CMGC Kinase Group". Cell Reports. 3 (4): 1306–1320. doi:10.1016/j.celrep.2013.03.027. PMID 23602568. 

Further reading[edit]