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Gene Review

SKY1  -  Sky1p

Saccharomyces cerevisiae S288c

Synonyms: SRPK, Serine/threonine-protein kinase SKY1, YM8261.10C, YMR216C
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Disease relevance of SKY1


High impact information on SKY1

  • Here, we demonstrate a novel function of the single conserved SR protein kinase Sky1p in nuclear import in budding yeast [3].
  • Strikingly, all RS domain-mediated interactions were abolished by SKY1 deletion and were rescuable by yeast or mammalian SR protein-specific kinases, indicating that phosphorylation has a far greater impact on RS domain interactions in vivo than in vitro [4].
  • Using a transcriptional repression assay, we further showed that most LexA-SR fusion proteins depend on Sky1p to efficiently recognize the LexA binding site in a reporter, suggesting that molecular targeting of RS domain-containing proteins within the nucleus was also affected [4].
  • The modeled complex combined with mutagenesis studies illustrate the molecular basis for substrate recognition by this kinase and suggest a mechanism by which SRPKs catalyze a sequential phosphorylation reaction of the consecutive RS dipeptide repeats characteristic of mammalian SRPK substrates [5].
  • Because of the strict splice site consensus and near absence of alternative splicing in Saccharomyces cerevisiae, it had been thought that budding yeast would lack an SRPK and its substrates [6].

Biological context of SKY1


Anatomical context of SKY1

  • Based on the modification of the anticancer drug sensitivity profile and our finding that sky1 Delta cells display a mutator phenotype, we propose that Sky1p might play a significant role in specific repair and/or tolerance pathways [2].

Associations of SKY1 with chemical compounds

  • SKY1 disruption results in dramatically reduced uptake of spermine, spermidine, and putrescine [9].
  • In conclusion, we identified NPR2 as a novel component involved in cell kill provoked by cisplatin and doxorubicin, and our data support the hypothesis that NPR2 and SKY1 may use mutual regulatory routes to mediate the cytotoxicity of these anticancer drugs [10].
  • Therefore, we generated yeast npr2Delta sky1Delta double-knockout cells and performed clonogenic survival assays for cisplatin and doxorubicin, which revealed that NPR2 and SKY1 (SR-protein-specific kinase from budding yeast) are epistatic [10].
  • We show here that deletion of SKY1 or PTK2 in trk1,2Delta cells increase spermine tolerance, implying Trk1,2p independent activity [7].
  • Moreover, using sucrose density gradient analysis, we provide evidence that the import receptor Mtr10p, but not the SR protein kinase Sky1p, is involved in the timely regulated release of Npl3p from polysome-associated mRNAs [11].

Enzymatic interactions of SKY1

  • Sky1p bound and phosphorylated Npl3 with a Km that was 2 orders of magnitude lower than a short peptide mimic representing the phosphorylation site and only proximal determinants [12].

Regulatory relationships of SKY1


Other interactions of SKY1


Analytical, diagnostic and therapeutic context of SKY1


  1. 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]
  2. Inactivation of the Saccharomyces cerevisiae SKY1 gene induces a specific modification of the yeast anticancer drug sensitivity profile accompanied by a mutator phenotype. Schenk, P.W., Boersma, A.W., Brok, M., Burger, H., Stoter, G., Nooter, K. Mol. Pharmacol. (2002) [Pubmed]
  3. Conserved SR protein kinase functions in nuclear import and its action is counteracted by arginine methylation in Saccharomyces cerevisiae. Yun, C.Y., Fu, X.D. J. Cell Biol. (2000) [Pubmed]
  4. Phosphorylation regulates in vivo interaction and molecular targeting of serine/arginine-rich pre-mRNA splicing factors. Yeakley, J.M., Tronchère, H., Olesen, J., Dyck, J.A., Wang, H.Y., Fu, X.D. J. Cell Biol. (1999) [Pubmed]
  5. The structure of Sky1p reveals a novel mechanism for constitutive activity. Nolen, B., Yun, C.Y., Wong, C.F., McCammon, J.A., Fu, X.D., Ghosh, G. Nat. Struct. Biol. (2001) [Pubmed]
  6. Conservation in budding yeast of a kinase specific for SR splicing factors. Siebel, C.W., Feng, L., Guthrie, C., Fu, X.D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Deletions of SKY1 or PTK2 in the Saccharomyces cerevisiae trk1Deltatrk2Delta mutant cells exert dual effect on ion homeostasis. Erez, O., Kahana, C. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  8. Evidence for a role of Sky1p-mediated phosphorylation in 3' splice site recognition involving both Prp8 and Prp17/Slu4. Dagher, S.F., Fu, X.D. RNA (2001) [Pubmed]
  9. Screening for modulators of spermine tolerance identifies Sky1, the SR protein kinase of Saccharomyces cerevisiae, as a regulator of polyamine transport and ion homeostasis. Erez, O., Kahana, C. Mol. Cell. Biol. (2001) [Pubmed]
  10. Anticancer drug resistance induced by disruption of the Saccharomyces cerevisiae NPR2 gene: a novel component involved in cisplatin- and doxorubicin-provoked cell kill. Schenk, P.W., Brok, M., Boersma, A.W., Brandsma, J.A., Den Dulk, H., Burger, H., Stoter, G., Brouwer, J., Nooter, K. Mol. Pharmacol. (2003) [Pubmed]
  11. Yeast shuttling SR proteins Npl3p, Gbp2p, and Hrb1p are part of the translating mRNPs, and Npl3p can function as a translational repressor. Windgassen, M., Sturm, D., Cajigas, I.J., González, C.I., Seedorf, M., Bastians, H., Krebber, H. Mol. Cell. Biol. (2004) [Pubmed]
  12. Chemical clamping allows for efficient phosphorylation of the RNA carrier protein Npl3. Aubol, B.E., Ungs, L., Lukasiewicz, R., Ghosh, G., Adams, J.A. J. Biol. Chem. (2004) [Pubmed]
  13. Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation. Gilbert, W., Siebel, C.W., Guthrie, C. RNA (2001) [Pubmed]
  14. Mechanism of polyamine tolerance in yeast: novel regulators and insights. Porat, Z., Wender, N., Erez, O., Kahana, C. Cell. Mol. Life Sci. (2005) [Pubmed]
  15. Identification of Gbp2 as a novel poly(A)+ RNA-binding protein involved in the cytoplasmic delivery of messenger RNAs in yeast. Windgassen, M., Krebber, H. EMBO Rep. (2003) [Pubmed]
  16. Cellular localization and phosphorylation of Hrb1p is independent of Sky1p. Porat, Z., Erez, O., Kahana, C. Biochim. Biophys. Acta (2006) [Pubmed]
  17. Nucleotide-induced conformational changes in the Saccharomyces cerevisiae SR protein kinase, Sky1p, revealed by X-ray crystallography. Nolen, B., Ngo, J., Chakrabarti, S., Vu, D., Adams, J.A., Ghosh, G. Biochemistry (2003) [Pubmed]
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