SRPK1: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Serine/threonine-protein kinase SRPK1''' is an [[enzyme]] that in humans is encoded by the ''SRPK1'' [[gene]].<ref name="pmid8208298">{{cite journal | vauthors = Gui JF, Lane WS, Fu XD | title = A serine kinase regulates intracellular localization of splicing factors in the cell cycle | journal = Nature | volume = 369 | issue = 6482 | pages = 678–82 | date = Jul 1994 | pmid = 8208298 | pmc =  | doi = 10.1038/369678a0 }}</ref><ref name="pmid10198174">{{cite journal | vauthors = Wang HY, Arden KC, Bermingham JR, Viars CS, Lin W, Boyer AD, Fu XD | title = Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes | journal = Genomics | volume = 57 | issue = 2 | pages = 310–5 | date = May 1999 | pmid = 10198174 | pmc = | doi = 10.1006/geno.1999.5770 }}</ref><ref name="entrez"/>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_SRPK1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1wak.
| PDB = {{PDB2|1wak}}, {{PDB2|1wbp}}
| Name = SFRS protein kinase 1
| HGNCid = 11305
| Symbol = SRPK1
| AltSymbols =; SFRSK1
| OMIM = 601939
| ECnumber = 
| Homologene = 74461
| MGIid = 106908
| GeneAtlas_image1 = PBB_GE_SRPK1_202199_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_SRPK1_202200_s_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0000074 |text = regulation of progression through cell cycle}} {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007059 |text = chromosome segregation}} {{GNF_GO|id=GO:0007243 |text = protein kinase cascade}} {{GNF_GO|id=GO:0008380 |text = RNA splicing}} {{GNF_GO|id=GO:0030154 |text = cell differentiation}} {{GNF_GO|id=GO:0050684 |text = regulation of mRNA processing}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6732
    | Hs_Ensembl = ENSG00000096063
    | Hs_RefseqProtein = NP_003128
    | Hs_RefseqmRNA = NM_003137
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 6
    | Hs_GenLoc_start = 35908789
    | Hs_GenLoc_end = 35996942
    | Hs_Uniprot = Q96SB4
    | Mm_EntrezGene = 20815
    | Mm_Ensembl = ENSMUSG00000004865
    | Mm_RefseqmRNA = NM_016795
    | Mm_RefseqProtein = NP_058075
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 17
    | Mm_GenLoc_start = 28317192
    | Mm_GenLoc_end = 28349639
    | Mm_Uniprot = Q3TTF9
  }}
}}
'''SFRS protein kinase 1''', also known as '''SRPK1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SRPK1 SFRS protein kinase 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6732| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a serine/arginine protein kinase specific for the [[SR protein|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.<ref name="entrez">{{cite web | title = Entrez Gene: SRPK1 SFRS protein kinase 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6732| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: SRPK1 SFRS protein kinase 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6732| accessdate = }}</ref>
}}


==References==
== Possible anti-cancer target ==
{{reflist|2}}
 
==Further reading==
Some cancers are vascular endothelial growth factor (VEGF) dependant (for [[angiogenesis]]). SRPK1 activates (phosphorylates) [[VEGF splicing factor]].
[[SRPK1 inhibitor]]s (e.g. 'SPHINX compounds' <ref>[http://exonate.com/wp-content/uploads/2014/07/Poster-BMS-April-2014.pdf Development of novel anti-angiogenic SRPK1 inhibitors]</ref>) are being investigated as treatments for prostate cancer.<ref>[http://www.sciencedaily.com/releases/2014/11/141110083723.htm Molecular breakthrough could halt spread of prostate cancer]</ref><ref name=Mavrou2014>{{cite journal |title=Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer. |year=2014 | pmid=25381816 | doi=10.1038/onc.2014.360 |journal=Oncogene |pmc=4351909 |volume=34 |pages=4311–9 |vauthors=Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, Gillatt DA, Ladomery MR, Harper SJ, Bates DO, Oltean S}}</ref>
 
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 inhibited tumor vasculature and growth.<ref>{{Cite web|url=http://www.gizmag.com/single-molecule-prostate-cancer/34686|title=Targeting a single molecule may stop prostate cancer in its tracks|last=Lavars|first=Nick|date=November 11, 2014|website=www.gizmag.com|access-date=2016-04-10}}</ref>
 
== Interactions ==
 
SRPK1 has been shown to [[Protein-protein interaction|interact]] with:
* [[ASF/SF2]]<ref name = pmid9472028/><ref name = pmid17517895>{{cite journal | vauthors = Lukasiewicz R, Velazquez-Dones A, Huynh N, Hagopian J, Fu XD, Adams J, Ghosh G | title = Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions | journal = J. Biol. Chem. | volume = 282 | issue = 32 | pages = 23036–43 | date = Aug 2007 | pmid = 17517895 | doi = 10.1074/jbc.M611305200 }}</ref><ref name = pmid12565863>{{cite journal | vauthors = Umehara H, Nishii Y, Morishima M, Kakehi Y, Kioka N, Amachi T, Koizumi J, Hagiwara M, Ueda K | title = Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A | journal = Biochem. Biophys. Res. Commun. | volume = 301 | issue = 2 | pages = 324–9 | date = Feb 2003 | pmid = 12565863 | doi =  10.1016/s0006-291x(02)03017-6}}</ref><ref name = pmid10196197>{{cite journal | vauthors = Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR, Hagiwara M | title = The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs) | journal = J. Biol. Chem. | volume = 274 | issue = 16 | pages = 11125–31 | date = Apr 1999 | pmid = 10196197 | doi =  10.1074/jbc.274.16.11125}}</ref> and
* [[SNRP70]].<ref name = pmid9472028>{{cite journal | vauthors = Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD | title = SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells | journal = J. Cell Biol. | volume = 140 | issue = 4 | pages = 737–50 | date = Feb 1998 | pmid = 9472028 | pmc = 2141757 | doi =  10.1083/jcb.140.4.737}}</ref><ref name = pmid12417631>{{cite journal | vauthors = Kamachi M, Le TM, Kim SJ, Geiger ME, Anderson P, Utz PJ | title = Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway | journal = J. Exp. Med. | volume = 196 | issue = 9 | pages = 1213–25 | date = Nov 2002 | pmid = 12417631 | pmc = 2194102 | doi =  10.1084/jem.20021167}}</ref>
* [[C6orf201]] <ref>{{cite journal|last1=Varjosalo|first1=Markku|last2=Keskitalo|first2=Salla|last3=Van Drogen|first3=Audrey|last4=Nurkkala|first4=Helka|last5=Vichalkovski|first5=Anton|last6=Aebersold|first6=Ruedi|last7=Gstaiger|first7=Matthias|title=The Protein Interaction Landscape of the Human CMGC Kinase Group|journal=Cell Reports|date=April 2013|volume=3|issue=4|pages=1306–1320|doi=10.1016/j.celrep.2013.03.027|pmid=23602568}}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Colwill K, Feng LL, Yeakley JM, Gish GD, Cáceres JF, Pawson T, Fu XD | title = SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors | journal = J. Biol. Chem. | volume = 271 | issue = 40 | pages = 24569–75 | year = 1996 | pmid = 8798720 | doi = 10.1074/jbc.271.40.24569 }}
| citations =
* {{cite journal | vauthors = Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD | title = SRPK2: A Differentially Expressed SR Protein-specific Kinase Involved in Mediating the Interaction and Localization of Pre-mRNA Splicing Factors in Mammalian Cells | journal = J. Cell Biol. | volume = 140 | issue = 4 | pages = 737–50 | year = 1998 | pmid = 9472028 | pmc = 2141757 | doi = 10.1083/jcb.140.4.737 }}
*{{cite journal | author=Gui JF, Lane WS, Fu XD |title=A serine kinase regulates intracellular localization of splicing factors in the cell cycle. |journal=Nature |volume=369 |issue= 6482 |pages= 678-82 |year= 1994 |pmid= 8208298 |doi= 10.1038/369678a0 }}
* {{cite journal | vauthors = Papoutsopoulou S, Nikolakaki E, Giannakouros T | title = SRPK1 and LBR protein kinases show identical substrate specificities | journal = Biochem. Biophys. Res. Commun. | volume = 255 | issue = 3 | pages = 602–7 | year = 1999 | pmid = 10049757 | doi = 10.1006/bbrc.1999.0249 }}
*{{cite journal  | author=Colwill K, Feng LL, Yeakley JM, ''et al.'' |title=SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors. |journal=J. Biol. Chem. |volume=271 |issue= 40 |pages= 24569-75 |year= 1996 |pmid= 8798720 |doi= }}
* {{cite journal | vauthors = Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR, Hagiwara M | title = The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs) | journal = J. Biol. Chem. | volume = 274 | issue = 16 | pages = 11125–31 | year = 1999 | pmid = 10196197 | doi = 10.1074/jbc.274.16.11125 }}
*{{cite journal | author=Wang HY, Lin W, Dyck JA, ''et al.'' |title=SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells. |journal=J. Cell Biol. |volume=140 |issue= 4 |pages= 737-50 |year= 1998 |pmid= 9472028 |doi= }}
* {{cite journal | vauthors = Paillard F | title = A novel soluble chimera for the treatment of familial hypercholesterolemia | journal = Hum. Gene Ther. | volume = 10 | issue = 7 | pages = 1093–4 | year = 1999 | pmid = 10340541 | doi = 10.1089/10430349950018085 }}
*{{cite journal | author=Papoutsopoulou S, Nikolakaki E, Giannakouros T |title=SRPK1 and LBR protein kinases show identical substrate specificities. |journal=Biochem. Biophys. Res. Commun. |volume=255 |issue= 3 |pages= 602-7 |year= 1999 |pmid= 10049757 |doi= 10.1006/bbrc.1999.0249 }}
* {{cite journal | vauthors = Papoutsopoulou S, Nikolakaki E, Chalepakis G, Kruft V, Chevaillier P, Giannakouros T | title = SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1 | journal = Nucleic Acids Res. | volume = 27 | issue = 14 | pages = 2972–80 | year = 1999 | pmid = 10390541 | pmc = 148514 | doi = 10.1093/nar/27.14.2972 }}
*{{cite journal | author=Koizumi J, Okamoto Y, Onogi H, ''et al.'' |title=The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs). |journal=J. Biol. Chem. |volume=274 |issue= 16 |pages= 11125-31 |year= 1999 |pmid= 10196197 |doi=  }}
* {{cite journal | vauthors = Nikolakaki E, Kohen R, Hartmann AM, Stamm S, Georgatsou E, Giannakouros T | title = Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B | journal = J. Biol. Chem. | volume = 276 | issue = 43 | pages = 40175–82 | year = 2001 | pmid = 11509566 | doi = 10.1074/jbc.M104755200 }}
*{{cite journal  | author=Wang HY, Arden KC, Bermingham JR, ''et al.'' |title=Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes. |journal=Genomics |volume=57 |issue= 2 |pages= 310-5 |year= 1999 |pmid= 10198174 |doi= 10.1006/geno.1999.5770 }}
* {{cite journal | vauthors = Daub H, Blencke S, Habenberger P, Kurtenbach A, Dennenmoser J, Wissing J, Ullrich A, Cotten M | title = Identification of SRPK1 and SRPK2 as the Major Cellular Protein Kinases Phosphorylating Hepatitis B Virus Core Protein | journal = J. Virol. | volume = 76 | issue = 16 | pages = 8124–37 | year = 2002 | pmid = 12134018 | pmc = 155132 | doi = 10.1128/JVI.76.16.8124-8137.2002 }}
*{{cite journal | author=Paillard F |title=A novel soluble chimera for the treatment of familial hypercholesterolemia. |journal=Hum. Gene Ther. |volume=10 |issue= 7 |pages= 1093-4 |year= 1999 |pmid= 10340541 |doi= 10.1089/10430349950018085 }}
* {{cite journal | vauthors = Kamachi M, Le TM, Kim SJ, Geiger ME, Anderson P, Utz PJ | title = Human Autoimmune Sera as Molecular Probes for the Identification of an Autoantigen Kinase Signaling Pathway | journal = J. Exp. Med. | volume = 196 | issue = 9 | pages = 1213–25 | year = 2003 | pmid = 12417631 | pmc = 2194102 | doi = 10.1084/jem.20021167 }}
*{{cite journal | author=Papoutsopoulou S, Nikolakaki E, Chalepakis G, ''et al.'' |title=SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1. |journal=Nucleic Acids Res. |volume=27 |issue= 14 |pages= 2972-80 |year= 1999 |pmid= 10390541 |doi= }}
* {{cite journal | vauthors = Mylonis I, Giannakouros T | title = Protein kinase CK2 phosphorylates and activates the SR protein-specific kinase 1 | journal = Biochem. Biophys. Res. Commun. | volume = 301 | issue = 3 | pages = 650–6 | year = 2003 | pmid = 12565829 | doi = 10.1016/S0006-291X(02)03055-3 }}
*{{cite journal | author=Nikolakaki E, Kohen R, Hartmann AM, ''et al.'' |title=Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B. |journal=J. Biol. Chem. |volume=276 |issue= 43 |pages= 40175-82 |year= 2001 |pmid= 11509566 |doi= 10.1074/jbc.M104755200 }}
* {{cite journal | vauthors = Aubol BE, Chakrabarti S, Ngo J, Shaffer J, Nolen B, Fu XD, Ghosh G, Adams JA | title = Processive phosphorylation of alternative splicing factor/splicing factor 2 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 22 | pages = 12601–6 | year = 2004 | pmid = 14555757 | pmc = 240664 | doi = 10.1073/pnas.1635129100 }}
*{{cite journal | author=Daub H, Blencke S, Habenberger P, ''et al.'' |title=Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein. |journal=J. Virol. |volume=76 |issue= 16 |pages= 8124-37 |year= 2002 |pmid= 12134018 |doi= }}
* {{cite journal | vauthors = Li J, Hawkins IC, Harvey CD, Jennings JL, Link AJ, Patton JG | title = Regulation of Alternative Splicing by SRrp86 and Its Interacting Proteins | journal = Mol. Cell. Biol. | volume = 23 | issue = 21 | pages = 7437–47 | year = 2003 | pmid = 14559993 | pmc = 207616 | doi = 10.1128/MCB.23.21.7437-7447.2003 }}
*{{cite journal | author=Kamachi M, Le TM, Kim SJ, ''et al.'' |title=Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway. |journal=J. Exp. Med. |volume=196 |issue= 9 |pages= 1213-25 |year= 2003 |pmid= 12417631 |doi=  }}
* {{cite journal | vauthors = Mylonis I, Drosou V, Brancorsini S, Nikolakaki E, Sassone-Corsi P, Giannakouros T | title = Temporal association of protamine 1 with the inner nuclear membrane protein lamin B receptor during spermiogenesis | journal = J. Biol. Chem. | volume = 279 | issue = 12 | pages = 11626–31 | year = 2004 | pmid = 14701833 | doi = 10.1074/jbc.M311949200 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Lee CG, Hague LK, Li H, Donnelly R | title = Identification of toposome, a novel multisubunit complex containing topoisomerase IIalpha | journal = Cell Cycle | volume = 3 | issue = 5 | pages = 638–47 | year = 2004 | pmid = 15034300 | doi = 10.4161/cc.3.5.825 }}
*{{cite journal | author=Mylonis I, Giannakouros T |title=Protein kinase CK2 phosphorylates and activates the SR protein-specific kinase 1. |journal=Biochem. Biophys. Res. Commun. |volume=301 |issue= 3 |pages= 650-6 |year= 2003 |pmid= 12565829 |doi= }}
* {{cite journal | vauthors = Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T | title = Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization | journal = Curr. Biol. | volume = 14 | issue = 16 | pages = 1436–50 | year = 2004 | pmid = 15324660 | doi = 10.1016/j.cub.2004.07.051 }}
*{{cite journal | author=Aubol BE, Chakrabarti S, Ngo J, ''et al.'' |title=Processive phosphorylation of alternative splicing factor/splicing factor 2. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue= 22 |pages= 12601-6 |year= 2004 |pmid= 14555757 |doi= 10.1073/pnas.1635129100 }}
*{{cite journal | author=Li J, Hawkins IC, Harvey CD, ''et al.'' |title=Regulation of alternative splicing by SRrp86 and its interacting proteins. |journal=Mol. Cell. Biol. |volume=23 |issue= 21 |pages= 7437-47 |year= 2003 |pmid= 14559993 |doi= }}
*{{cite journal  | author=Mungall AJ, Palmer SA, Sims SK, ''et al.'' |title=The DNA sequence and analysis of human chromosome 6. |journal=Nature |volume=425 |issue= 6960 |pages= 805-11 |year= 2003 |pmid= 14574404 |doi= 10.1038/nature02055 }}
*{{cite journal | author=Mylonis I, Drosou V, Brancorsini S, ''et al.'' |title=Temporal association of protamine 1 with the inner nuclear membrane protein lamin B receptor during spermiogenesis. |journal=J. Biol. Chem. |volume=279 |issue= 12 |pages= 11626-31 |year= 2004 |pmid= 14701833 |doi= 10.1074/jbc.M311949200 }}
*{{cite journal | author=Lee CG, Hague LK, Li H, Donnelly R |title=Identification of toposome, a novel multisubunit complex containing topoisomerase IIalpha. |journal=Cell Cycle |volume=3 |issue= 5 |pages= 638-47 |year= 2004 |pmid= 15034300 |doi= }}
*{{cite journal | author=Jin J, Smith FD, Stark C, ''et al.'' |title=Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. |journal=Curr. Biol. |volume=14 |issue= 16 |pages= 1436-50 |year= 2004 |pmid= 15324660 |doi= 10.1016/j.cub.2004.07.051 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{PDB Gallery|geneid=6732}}
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Revision as of 17:35, 16 November 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Serine/threonine-protein kinase SRPK1 is an enzyme that in humans is encoded by the SRPK1 gene.[1][2][3]

Function

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.[3]

Possible anti-cancer target

Some cancers are vascular endothelial growth factor (VEGF) dependant (for angiogenesis). SRPK1 activates (phosphorylates) VEGF splicing factor. SRPK1 inhibitors (e.g. 'SPHINX compounds' [4]) are being investigated as treatments for prostate cancer.[5][6]

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 inhibited tumor vasculature and growth.[7]

Interactions

SRPK1 has been shown to interact with:

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 3.0 3.1 "Entrez Gene: SRPK1 SFRS protein kinase 1".
  4. ↑ Development of novel anti-angiogenic SRPK1 inhibitors
  5. ↑ Molecular breakthrough could halt spread of prostate cancer
  6. ↑ Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, Gillatt DA, Ladomery MR, Harper SJ, Bates DO, Oltean S (2014). "Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer". Oncogene. 34: 4311–9. doi:10.1038/onc.2014.360. PMC 4351909. PMID 25381816.
  7. ↑ Lavars, Nick (November 11, 2014). "Targeting a single molecule may stop prostate cancer in its tracks". www.gizmag.com. Retrieved 2016-04-10.
  8. ↑ 8.0 8.1 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 2141757. PMID 9472028.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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 2194102. PMID 12417631.
  13. ↑ 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

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