Gli protein activity is controlled by multisite phosphorylation in vertebrate hedgehog signaling

Cell Reports

Volumn 6, Issue 1, 2014, Pages 168-181

  Niewiadomski, Pawel ^a,c   Kong, JenniferH ^b   Ahrends, Robert ^a,d   Ma, Yan ^a   Humke, EricW ^a   Khan, Sohini ^a   Teruel, MaryN ^a   Novitch, BennettG ^b   Rohatgi, Rajat ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c NENCKI INSTITUTE OF EXPERIMENTAL BIOLOGY   (Poland)

^d LEIBNIZ INSTITUT FÜR ANALYTISCHE WISSENSCHAFTEN ISAS E V   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP DEPENDENT PROTEIN KINASE; GLI PROTEIN; SERINE; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; THREONINE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GLI2; TRANSCRIPTION FACTOR GLI3; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; EMBRYO; IN VITRO STUDY; MULTISITE PHOSPHORYLATION; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS INHIBITION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; SPINAL CORD DEVELOPMENT; TRANSCRIPTION REGULATION;

ERINACEIDAE; VERTEBRATA;

ANIMALS; CHICK EMBRYO; CYCLIC AMP-DEPENDENT PROTEIN KINASES; HEDGEHOG PROTEINS; HEK293 CELLS; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; MICE; NERVE TISSUE PROTEINS; NIH 3T3 CELLS; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; SERINE; SIGNAL TRANSDUCTION;

EID: 84892542938     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2013.12.003     Document Type: Article

References (56)

1. Abell E., Ahrends R., Bandara S., Park B.O., Teruel M.N. Parallel adaptive feedback enhances reliability of the Ca2+ signaling system. Proc. Natl. Acad. Sci. USA 2011, 108:14485-14490.
2. Asaoka Y., Kanai F., Ichimura T., Tateishi K., Tanaka Y., Ohta M., Seto M., Tada M., Ijichi H., Ikenoue T., et al. Identification of a suppressive mechanism for Hedgehog signaling through a novel interaction of Gli with 14-3-3. J.Biol. Chem. 2010, 285:4185-4194.
3. Bai C.B., Stephen D., Joyner A.L. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev. Cell 2004, 6:103-115.
4. Aza-Blanc P., Ramírez-Weber F.A., Laget M.P., Schwartz C., Kornberg T.B. Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell 1997, 89:1043-1053.
5. Bok J., Dolson D.K., Hill P., Rüther U., Epstein D.J., Wu D.K. Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear. Development 2007, 134:1713-1722.
6. Briscoe J., Thérond P.P. The mechanisms of Hedgehog signallingand its roles in development and disease. Nat. Rev. Mol. Cell Biol. 2013, 14:416-429.
7. Briscoe J., Chen Y., Jessell T.M., Struhl G. A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube. Mol. Cell 2001, 7:1279-1291.
8. Corbit K.C., Aanstad P., Singla V., Norman A.R., Stainier D.Y.R., Reiter J.F. Vertebrate Smoothened functions at the primary cilium. Nature 2005, 437:1018-1021.
9. Cox D.M., Zhong F., Du M., Duchoslav E., Sakuma T., McDermott J.C. Multiple reaction monitoring as a method for identifying protein posttranslational modifications. J.Biomol. Tech. 2005, 16:83-90.
10. Dorn K.V., Hughes C.E., Rohatgi R. A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia. Dev. Cell 2012, 23:823-835.
11. Epstein D.J., Marti E., Scott M.P., McMahon A.P. Antagonizing cAMP-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathway. Development 1996, 122:2885-2894.
12. Fan C.M., Porter J.A., Chiang C., Chang D.T., Beachy P.A., Tessier-Lavigne M. Long-range sclerotome induction by sonic hedgehog: direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway. Cell 1995, 81:457-465.
13. Fuccillo M., Rallu M., McMahon A.P., Fishell G. Temporal requirement for hedgehog signaling in ventral telencephalic patterning. Development 2004, 131:5031-5040.
14. Gerber S.A., Rush J., Stemman O., Kirschner M.W., Gygi S.P. Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc. Natl. Acad. Sci. USA 2003, 100:6940-6945.
15. Hahn H., Wicking C., Zaphiropoulous P.G., Gailani M.R., Shanley S., Chidambaram A., Vorechovsky I., Holmberg E., Unden A.B., Gillies S., et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996, 85:841-851.
16. Hammerschmidt M., Bitgood M.J., McMahon A.P. Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo. Genes Dev. 1996, 10:647-658.
17. Hill P., Wang B., Rüther U. The molecular basis of Pallister Hall associated polydactyly. Hum. Mol. Genet. 2007, 16:2089-2096.
18. Hui C.-C., Angers S. Gli proteins in development and disease. Annu. Rev. Cell Dev. Biol. 2011, 27:513-537.
19. Humke E.W., Dorn K.V., Milenkovic L., Scott M.P., Rohatgi R. The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins. Genes Dev. 2010, 24:670-682.
20. Hynes M., Porter J.A., Chiang C., Chang D., Tessier-Lavigne M., Beachy P.A., Rosenthal A. Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron 1995, 15:35-44.
21. Jiang J., Struhl G. Protein kinase A and hedgehog signaling in Drosophila limb development. Cell 1995, 80:563-572.
22. Kang S., Graham J.M., Olney A.H., Biesecker L.G. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nat. Genet. 1997, 15:266-268.
23. Kim J., Kato M., Beachy P.A. Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus. Proc. Natl. Acad. Sci. USA 2009, 106:21666-21671.
24. Lee C.W., Ferreon J.C., Ferreon A.C.M., Arai M., Wright P.E. Graded enhancement of p53 binding to CREB-binding protein (CBP) by multisite phosphorylation. Proc. Natl. Acad. Sci. USA 2010, 107:19290-19295.
25. Lei Q., Zelman A.K., Kuang E., Li S., Matise M.P. Transduction of graded Hedgehog signaling by a combination of Gli2 and Gli3 activator functions in the developing spinal cord. Development 2004, 131:3593-3604.
26. Lepage T., Cohen S.M., Diaz-Benjumea F.J., Parkhurst S.M. Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning. Nature 1995, 373:711-715.
27. Li W., Ohlmeyer J.T., Lane M.E., Kalderon D. Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development. Cell 1995, 80:553-562.
28. Mayya V., Rezual K., Wu L., Fong M.B., Han D.K. Absolute quantification of multisite phosphorylation by selective reaction monitoring mass spectrometry: determination of inhibitory phosphorylation status of cyclin-dependent kinases. Mol. Cell. Proteomics 2006, 5:1146-1157.
29. Méthot N., Basler K. Hedgehog controls limb development by regulating the activities of distinct transcriptional activator and repressor forms of Cubitus interruptus. Cell 1999, 96:819-831.
30. Méthot N., Basler K. An absolute requirement for Cubitus interruptus in Hedgehog signaling. Development 2001, 128:733-742.
31. Niewiadomski P., Zhujiang A., Youssef M., Waschek J.A. Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA. Cell. Signal. 2013, 25:2222-2230.
32. Novitch B.G., Chen A.I., Jessell T.M. Coordinate regulation of motor neuron subtype identity and pan-neuronal properties by the bHLH repressor Olig2. Neuron 2001, 31:773-789.
33. Okamura H., Aramburu J., García-Rodríguez C., Viola J.P., Raghavan A., Tahiliani M., Zhang X., Qin J., Hogan P.G., Rao A. Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity. Mol. Cell 2000, 6:539-550.
34. Pan D., Rubin G.M. cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs. Cell 1995, 80:543-552.
35. Pan Y., Bai C.B., Joyner A.L., Wang B. Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol. Cell. Biol. 2006, 26:3365-3377.
36. Pan Y., Wang C., Wang B. Phosphorylation of Gli2 by protein kinase A is required for Gli2 processing and degradation and the Sonic Hedgehog-regulated mouse development. Dev. Biol. 2009, 326:177-189.
37. Park K.-S., Mohapatra D.P., Misonou H., Trimmer J.S. Graded regulation of the Kv2.1 potassium channel by variable phosphorylation. Science 2006, 313:976-979.
38. Price M.A., Kalderon D. Proteolysis of cubitus interruptus in Drosophila requires phosphorylation by protein kinase A. Development 1999, 126:4331-4339.
39. Pufall M.A., Lee G.M., Nelson M.L., Kang H.-S., Velyvis A., Kay L.E., McIntosh L.P., Graves B.J. Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region. Science 2005, 309:142-145.
40. Ribes V., Balaskas N., Sasai N., Cruz C., Dessaud E., Cayuso J., Tozer S., Yang L.L., Novitch B., Marti E., Briscoe J. Distinct Sonic Hedgehog signaling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube. Genes Dev. 2010, 24:1186-1200.
41. Riobó N.A., Lu K., Ai X., Haines G.M., Emerson C.P. Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling. Proc. Natl. Acad. Sci. USA 2006, 103:4505-4510.
42. Salazar C., Höfer T. Multisite protein phosphorylation-from molecular mechanisms to kinetic models. FEBS J. 2009, 276:3177-3198.
43. Sasaki H., Hui C., Nakafuku M., Kondoh H. A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh invitro. Development 1997, 124:1313-1322.
44. Sasaki H., Nishizaki Y., Hui C., Nakafuku M., Kondoh H. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development 1999, 126:3915-3924.
45. Stamataki D., Ulloa F., Tsoni S.V., Mynett A., Briscoe J. A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural tube. Genes Dev. 2005, 19:626-641.
46. Strutt D.I., Wiersdorff V., Mlodzik M. Regulation of furrow progression in the Drosophila eye by cAMP-dependent protein kinase A. Nature 1995, 373:705-709.
47. Tempé D., Casas M., Karaz S., Blanchet-Tournier M.-F., Concordet J.-P. Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP. Mol. Cell. Biol. 2006, 26:4316-4326.
48. Thomson M., Gunawardena J. Unlimited multistability in multisite phosphorylation systems. Nature 2009, 460:274-277.
49. Torres J.Z., Miller J.J., Jackson P.K. High-throughput generation of tagged stable cell lines for proteomic analysis. Proteomics 2009, 9:2888-2891.
50. Tukachinsky H., Lopez L.V., Salic A. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. J.Cell Biol. 2010, 191:415-428.
51. Tuson M., He M., Anderson K.V. Protein kinase A acts at the basal body of the primary cilium to prevent Gli2 activation and ventralization of the mouse neural tube. Development 2011, 138:4921-4930.
52. Wang B., Li Y. Evidence for the direct involvement of betaTrCP in Gli3 protein processing. Proc. Natl. Acad. Sci. USA 2006, 103:33-38.
53. Wang G., Wang B., Jiang J. Protein kinase A antagonizes Hedgehog signaling by regulating both the activator and repressor forms of Cubitus interruptus. Genes Dev. 1999, 13:2828-2837.
54. Wang B., Fallon J.F., Beachy P.A. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 2000, 100:423-434.
55. Wen X., Lai C.K., Evangelista M., Hongo J.-A., de Sauvage F.J., Scales S.J. Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation. Mol. Cell. Biol. 2010, 30:1910-1922.
56. Zhou C., Jacobsen F.W., Cai L., Chen Q., Shen W.D. Development of a novel mammalian cell surface antibody display platform. MAbs 2010, 2:508-518.