Skip to main content
SpringerLink
Log in

The evolutionary strata of DARPP-32 tail implicates hierarchical functional expansion in higher vertebrates

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

DARPP-32 (dopamine and adenosine 3′,5′-monophosphate-regulated phosphoprotein of 32 kDa), which belongs to PPP1R1 gene family, is known to act as an important integrator in dopamine-mediated neurotransmission via the inhibition of protein phosphatase-1 (PP1). Besides its neuronal roles, this protein also behaves as a key player in pathological and pharmacological aspects. Use of bioinformatics and phylogenetics approaches to further characterize the molecular features of DARPP-32 can guide future works. Predicted phosphorylation sites on DARPP-32 show conservation across vertebrates. Phylogenetics analysis indicates evolutionary strata of phosphorylation site acquisition at the C-terminus, suggesting functional expansion of DARPP-32, where more diverse signalling cues may involve in regulating DARPP-32 in inhibiting PP1 activity. Moreover, both phylogenetics and synteny analyses suggest de novo origination of PPP1R1 gene family via chromosomal rearrangement and exonization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Aitken A, Bilham T and Cohen P 1982 Complete primary structure of protein phosphatase inhibitor-1 from rabbit skeletal muscle. Eur. J. Biochem. 126 235–246

  • Albert KA, Hemmings HC Jr, Adamo AI, Potkin SG, Akbarian S, Sandman CA, Cotman CW, Bunney WE Jr and Greengard P 2002 Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia. Arch. Gen. Psychiatry 59 705–712

    Article  CAS  PubMed  Google Scholar 

  • Alpy F and Tomasetto C 2006 MLN64 and MENTHO, two mediators of endosomal cholesterol transport. Biochem. Soc. Trans. 34: 343–345

    Article  CAS  PubMed  Google Scholar 

  • Belkhiri A, Dar AA, Zaika A, Kelley M and El-Rifai W 2008 t-Darpp promotes cancer cell survival by up-regulation of Bcl2 through Akt-dependent mechanism. Cancer Res. 68 395–403

    Article  CAS  PubMed  Google Scholar 

  • Benderska N, Becker K, Girault JA, Becker CM, Andreadis A and Stamm S 2010 DARPP-32 binds to tra2-beta1 and influences alternative splicing. Biochim. Biophys. Acta 1799 448–453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bibb JA, Snyder GL, Nishi A, Yan Z, Meijer L, Fienberg AA, Tsai LH, Kwon YT, Girault JA, Czernik AJ, Huganir RL, Hemmings HC Jr, Nairn AC and Greengard P 1999 Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature 402 669–671

    Article  CAS  PubMed  Google Scholar 

  • Bollen M, Peti W, Ragusa MJ and Beullens M 2010 The extended PP1 toolkit: designed to create specificity. Trends Biochem. Sci. 35 450–458

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ceulemans H, Stalmans W and Bollen M 2002 Regulator-driven functional diversification of protein phosphatase-1 in eukaryotic evolution. BioEssays 24 371–381

    Article  CAS  PubMed  Google Scholar 

  • Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG and Thompson JD 2003 Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res. 31 3497–3500

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chocarro-Calvo A, Zaballos MA, Santisteban P and García-Jiménez C 2012 DARPP-32 is required for MAPK/ERK signaling in thyroid cells. Mol. Endocrinol. 26 471–480

  • Dancheck B, Nairn AC and Peti W 2008 Detailed structural characterization of unbound protein phosphatase 1 inhibitors. Biochemistry 47 12346–12356

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Egloff MP, Johnson DF, Moorhead G, Cohen PT, Cohen P and Barford D 1997 Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1. EMBO J 16 1876–1887

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fernandez É, Schiappa R, Girault J-A and Le Novère N 2006 DARPP-32 Is a robust integrator of dopamine and glutamate signals. PLoS Comput. Biol. 2 e176

    Article  PubMed Central  PubMed  Google Scholar 

  • Goldberg J, Huang HB, Kwon YG, Greengard P, Nairn AC and Kuriyan J 1995 Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature 376 745–753

    Article  CAS  PubMed  Google Scholar 

  • Hemmings HC Jr and Greengard P 1986 DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein: regional, tissue, and phylogenetic distribution. J. Neurosci. 6 1469–1481

    CAS  PubMed  Google Scholar 

  • Hemmings HC Jr, Girault JA, Nairn AC, Bertuzzi G and Greengard P 1992 Distribution of protein phosphatase inhibitor-1 in brain and peripheral tissues of various species: comparison with DARPP-32. J. Neurochem. 59 1053–1061

    Article  CAS  PubMed  Google Scholar 

  • Hemmings HC Jr, Nairn AC, Aswad DW and Greengard P 1984 DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. II. Purification and characterization of the phosphoprotein from bovine caudate nucleus. J. Neurosci. 4 99–110

    CAS  PubMed  Google Scholar 

  • Jones DT 1999 Protein secondary structure prediction based on position-specific scoring matrices. J. Mol. Biol. 292 195–202

    Article  CAS  PubMed  Google Scholar 

  • Katoh K, Misawa K, Kuma K and Miyata T 2002 MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res. 30 3059–3066

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Krieger E, Koraimann G and Vriend G 2002 Increasing the precision of comparative models with YASARA NOVA—a self-parameterizing force field. Proteins 47 393–402

    Article  CAS  PubMed  Google Scholar 

  • Marsh JA, Dancheck B, Ragusa MJ, Allaire M, Forman-Kay JD and Peti W 2010 Structural diversity in free and bound states of intrinsically disordered protein phosphatase 1 regulators. Structure 18 1094–1103

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Meister B, Fryckstedt J, Schalling M, Cortés R, Hökfelt T, Aperia A, Hemmings HC Jr, Nairn AC, Ehrlich M and Greengard P 1989 Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells. Proc. Natl. Acad. Sci. USA 86 8068–8072

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Moorhead GB, Trinkle-Mulcahy L and Ulke-Lemée A 2007 Emerging roles of nuclear protein phosphatases. Nat. Rev. Mol. Cell Biol. 8 234–244

    Article  CAS  PubMed  Google Scholar 

  • Neyroz P, Desdouits F, Benfenati F, Knutson JR, Greengard P and Girault JA 1993 Study of the conformation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by fluorescence spectroscopy. J. Biol. Chem. 268 24022–24031

    CAS  PubMed  Google Scholar 

  • Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S and Mann M 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal 3 ra3

    Article  PubMed  Google Scholar 

  • Ouimet CC, Miller PE, Hemmings HC Jr, Walaas SI and Greengard P 1984 DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization. J. Neurosci. 4 111–124

    CAS  PubMed  Google Scholar 

  • Stipanovich A, Valjent E, Matamales M, Nishi A, Ahn JH, Maroteaux M, Bertran-Gonzalez J, Brami-Cherrier K, Enslen H, Corbillé AG, Filhol O, Nairn AC, Greengard P, Hervé D and Girault JA 2008 A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature 453 879–884

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stone RA, Laties AM, Hemmings HC Jr, Ouimet CC and Greengard P 1986 DARPP-32 in the ciliary epithelium of the eye: a neurotransmitter-regulated phosphoprotein of brain localizes to secretory cells. J. Histochem. Cytochem. 34 1465–1468

    Article  CAS  PubMed  Google Scholar 

  • Svenningsson P, Nairn AC and Greengard P 2005 DARPP-32 mediates the actions of multiple drugs of abuse. AAPS J 7 E353–E360

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Svenningsson P, Nishi A, Fisone G, Girault JA, Nairn AC and Greengard P 2004 DARPP-32: an integrator of neurotransmission. Annu. Rev. Pharmacol. Toxicol. 44 269–296

    Article  CAS  PubMed  Google Scholar 

  • Tamura K, Peterson D, Peterson N, Stecher G, Nei M and Kumar S 2011 MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28 2731–2739

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ubersax JA and Ferrell JE Jr 2007 Mechanisms of specificity in protein phosphorylation. Nat. Rev. Mol. Cell. Biol. 8 530–541

    Article  CAS  PubMed  Google Scholar 

  • Valjent E, Pascoli V, Svenningsson P, Paul S, Enslen H, Corvol JC, Stipanovich A, Caboche J, Lombroso PJ, Nairn AC, Greengard P, Hervé D and Girault JA 2005 Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proc. Natl. Acad. Sci. USA 102 491–496

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Van de Peer Y, Maere S and Meyer A 2009 The evolutionary significance of ancient genome duplications. Nat. Rev. Genet. 10 725–732

    Article  PubMed  Google Scholar 

  • Vangamudi B, Peng DF, Cai Q, El-Rifai W, Zheng W and Belkhiri A 2010 t-DARPP regulates phosphatidylinositol-3-kinase-dependent cell growth in breast cancer. Mol. Cancer 9 240

    Article  PubMed Central  PubMed  Google Scholar 

  • Vangamudi B, Zhu S, Soutto M, Belkhiri A and El-Rifai W 2011 Regulation of β-catenin by t-DARPP in upper gastrointestinal cancer cells. Mol. Cancer 10 32

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Walaas SI, Aswad DW and Greengard P 1983 A dopamine- and cyclic AMP-regulated phosphoprotein enriched in dopamine-innervated brain regions. Nature 301 69–71

    Article  CAS  PubMed  Google Scholar 

  • Xue Y, Zhou F, Zhu M, Ahmed K, Chen G and Yao X 2005 GPS: a comprehensive www server for phosphorylation sites prediction. Nucleic Acids Res. 33 W184–W187

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yger M and Girault JA 2011 DARPP-32, Jack of All Trades… Master of Which? Front. Behav. Neurosci. 5 56

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou FF, Xue Y, Chen GL and Yao X 2004 GPS: a novel group-based phosphorylation predicting and scoring method. Biochem. Biophys. Res. Commun. 325 1443–1448

    Article  CAS  PubMed  Google Scholar 

  • Zhu S, Belkhiri A and El-Rifai W 2011 DARPP-32 increases interactions between epidermal growth factor receptor and ERBB3 to promote tumour resistance to gefitinib. Gastroenterology 141 1738–1748

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

This research work was supported by University of Malaya UMRG research grants RG163/09HTM and RG523/13HTM.

Author information

Authors and Affiliations

  1. Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Choong Yong Ung & Teow Chong Teoh

Authors
  1. Choong Yong Ung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Teow Chong Teoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teow Chong Teoh.

Additional information

Corresponding editor: Stuart A Newman

[Ung CY and Teoh TC 2014 The evolutionary strata of DARPP-32 tail implicates hierarchical functional expansion in higher vertebrates. J. Biosci. 39 1–12] DOI 10.1007/s12038-014-9438-8

Supplementary materials pertaining to this article are available on the Journal of Biosciences Website at http://www.ias.ac.in/jbiosci/jun2014/supp/Ung.pdf

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 33.0 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ung, C.Y., Teoh, T.C. The evolutionary strata of DARPP-32 tail implicates hierarchical functional expansion in higher vertebrates. J Biosci 39, 493–504 (2014). https://doi.org/10.1007/s12038-014-9438-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-014-9438-8

Keywords

Search

Navigation