Networks for the allosteric control of protein kinases

Current Opinion in Structural Biology

Volumn 16, Issue 6, 2006, Pages 686-692

  Shi, Zhengshuang ^a   Resing, Katheryn A ^a   Ahn, Natalie G ^a  

^a UNIVERSITY OF COLORADO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AURORA A KINASE; AURORA B KINASE; BINDING PROTEIN; DOCKING PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; PROTEIN TYROSINE KINASE; REGULATOR PROTEIN; SCAFFOLD PROTEIN;

ALLOSTERISM; CRYSTAL STRUCTURE; DEUTERIUM HYDROGEN EXCHANGE; DIMERIZATION; ENZYME ACTIVITY; ENZYME SPECIFICITY; MASS SPECTROMETRY; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN PHOSPHORYLATION; REVIEW;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; DEUTERIUM; DIMERIZATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HYDROGEN; MASS SPECTROMETRY; MODELS, BIOLOGICAL; MODELS, MOLECULAR; PROTEIN KINASES; PROTEIN STRUCTURE, QUATERNARY; SIGNAL TRANSDUCTION;

EID: 33847061197     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.sbi.2006.10.011     Document Type: Review

References (49)

1. Johnson L.N., Noble M.E.M., and Owen D.J. Active and inactive protein kinases: structural basis for regulation. Cell 85 (1996) 149-158
2. Huse M., and Kuriyan J. The conformational plasticity of protein kinases. Cell 109 (2002) 275-282
3. Nolen B., Taylor S., and Ghosh G. Regulation of protein kinases: controlling activity through activation segment conformation. Mol Cell 15 (2004) 661-675
4. Goldsmith E.J. Allosteric enzymes as models for chemomechanical energy transducing assemblies. FASEB J 10 (1996) 702-708
5. Johnson D.A., Akamine P., Radzio-Andzelm E., Madhusudan M., and Taylor S.S. Dynamics of cAMP-dependent protein kinase. Chem Rev 101 (2001) 2243-2270
6. Jeffrey P.D., Ruso A.A., Polyak K., Gibbs E., Hurwitz J., Massague J., and Pavletich N.P. Mechanism of Cdk activation revealed by the structure of a cyclinA-Cdk2 complex. Nature 376 (1995) 313-320
7. Honda R., Lowe E.D., Dubinina E., Skamnaki V., Cook A., Brown N.R., and Johnson L.N. The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles. EMBO J 24 (2005) 452-463
8. Yang J., Cron P., Thompson V., Good V.M., Hess D., Hemmings B.A., and Barford D. Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation. Mol Cell 9 (2002) 1227-1240
9. Gonfloni S., Weijland A., Kretzschmar J., and Superti-Furga G. Crosstalk between the catalytic and regulatory domains allows bidirectional regulation of Src. Nat Struct Biol 7 (2000) 281-286
10. Carmena M., and Earnshaw W.C. The cellular geography of Aurora kinases. Nat Rev Mol Cell Biol 4 (2003) 842-854
11. Eyers P.A., Erikson E., Chen L.G., and Maller J.L. A novel mechanism for activation of the protein kinase Aurora A. Curr Biol 13 (2003) 691-697
12. Bayliss R., Sardon T., Vernos I., and Conti E. Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell 12 (2003) 851-862. This study reports the co-crystal structure of Aurora A and a segment of its activator, TPX2. Activation occurs by TPX2 binding to a region upstream of the activation lip. This triggers a lever-arm movement to displace the lip, switching a phosphothreonine residue to a buried conformation and locking the lip in an active conformation.
13. Bishop J.D., and Schumacher J.M. Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B kinase stimulates Aurora B kinase activity. J Biol Chem 277 (2002) 27577-27580
14. Sessa F., Mapelli M., Ciferri C., Tarricone C., Areces L.B., Schneider T.R., Stukenberg R.T., and Musacchio A. Mechanism of Aurora B activation by INCENP and inhibition by Hesperadin. Mol Cell 18 (2005) 379-391. An X-ray structure of the Aurora B-INCENP complex shows interactions over a large surface area of the kinase N terminus. Partial activation is achieved by indirect interactions that switch the activation lip into an extended, active conformation, but impair formation of the Lys-Glu ion pair.
15. Hubbard S.R. Juxtamembrane autoinhibition in receptor tyrosine kinases. Nat Rev Mol Cell Biol 5 (2004) 464-470
16. Zhang X.W., Gureasko J., Shen K., Cole P.A., and Kuriyan J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 125 (2006) 1137-1149. A new X-ray structure of EGFR reveals a novel mechanism for activation through formation of an asymmetric dimer. The activation lip of one monomer adopts an active conformation through the interaction of helix αC with the C-terminal lobe of another monomer.
17. Hinnebusch A.G. eIF2 alpha kinases provide a new solution to the puzzle of substrate specificity. Nat Struct Biol 12 (2005) 835-838
18. Dar A.C., Dever T.E., and Sicheri F. Higher-order substrate recognition of elF2 alpha by the RNA-dependent protein kinase PKR. Cell 122 (2005) 887-900. The structure of the catalytic domain of PKR in complex with eIF2α reveals an allosteric activation mechanism in which kinase dimerization, autophosphorylation and substrate binding are coupled. This represents the only X-ray structure so far for a kinase co-crystallized with a full-length substrate.
19. ••], combines structural analysis and mutagenesis to reveal a mechanism in which N-terminal dimerization controls the activation lip conformation via helix αC. Rearrangement of the lip subsequently leads to C-terminal reorganization, facilitating substrate binding.
20. Qiu H.F., Hu C.H., Dong J.S., and Hinnebusch A.G. Mutations that bypass tRNA binding activate the intrinsically defective kinase domain in GCN2. Genes Dev 16 (2002) 1271-1280
21. Padyana A.K., Qiu H.F., Roll-Mecak A., Hinnebusch A.G., and Burley S.K. Structural basis for autoinhibition and mutational activation of eukaryotic initiation factor 2 alpha protein kinase GCN2. J Biol Chem 280 (2005) 29289-29299. The crystal structure of GCN2 in wild-type and active mutant forms reveals the critical role of interdomain interactions in kinase activity. The study suggests that activation by the Arg794Gly mutation involves the release of constraints within the hinge region, enhancing active site accessibility.
22. Biondi R.M., and Nebreda A.R. Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions. Biochem J 372 (2003) 1-13
23. Chang C.I., Xu B.E., Akella R., Cobb M.H., and Goldsmith E.J. Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b. Mol Cell 9 (2002) 1241-1249
24. Lee T., Hoofnagle A.N., Kabuyama Y., Stroud J., Min X.S., Goldsmith E.J., Chen L., Resing K.A., and Ahn N.G. Docking motif interactions in MAP kinases revealed by hydrogen exchange mass spectrometry. Mol Cell 14 (2004) 43-55
25. Zhou T.J., Sun L.G., Humphreys J., and Goldsmith E.J. Docking interactions induce exposure of activation loop in the MAP kinase ERK2. Structure 14 (2006) 1011-1019. X-ray structures of ERK2 in complex with docking motif peptides from HePTP or MEK2 reveal a distinct conformation of the activation lip compared to that in the active and inactive forms. This shows that occupancy of the docking-motif-binding site can allosterically control the structure of the active site.
26. Bhattacharyya R.P., Remenyi A., Good M.C., Bashor C.J., Falick A.M., and Lim W.A. The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway. Science 311 (2006) 822-826. This structural study shows that a fragment of the scaffolding protein Ste5 binds to Fus3 in a bipartite manner. Ste5 is also found to activate Fus3 by enhancing the autophosphorylation rate, possibly through control of interlobal interactions. The findings suggest that Ste5 may play an active role as an allosteric regulator of the yeast mating pathway.
27. Heo J.S., Kim S.K., Seo C.I., Kim Y.K., Sung B.J., Lee H.S., Lee J.I., Park S.Y., Kim J.H., Hwang K.Y., et al. Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125. EMBO J 23 (2004) 2185-2195. The crystal structure of JNK1 complexed with its scaffold, JIP1, suggests that JIP1 blocks JNK1 activity by constraining hinge motions, and N- and C-terminal domain interactions.
28. Elion E.A. The Ste5p scaffold. J Cell Sci 114 (2001) 3967-3978
29. Hoofnagle A.N., Resing K.A., and Ahn N.G. Protein analysis by hydrogen exchange mass spectrometry. Annu Rev Biophys Biomol Struct 32 (2003) 1-25
30. Resing K.A., and Ahn N.G. Deuterium exchange mass spectrometry as a probe of protein kinase activation. Analysis of wild-type and constitutively active mutants of MAP kinase kinase-1. Biochemistry 37 (1998) 463-475
31. Delaney A.M., Printen J.A., Chen H.F., Fauman E.B., and Dudley D.T. Identification of a novel mitogen-activated protein kinase kinase activation domain recognized by the inhibitor PD 184352. Mol Cell Biol 22 (2002) 7593-7602
32. Ohren J.F., Chen H.F., Pavlovsky A., Whitehead C., Zhang E.L., Kuffa P., Yan C.H., McConnell P., Spessard C., Banotai C., et al. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat Struct Mol Biol 11 (2004) 1192-1197
33. Lee T., Hoofnagle A.N., Resing K.A., and Ahn N.G. Hydrogen exchange solvent protection by an ATP analogue reveals conformational changes in ERK2 upon activation. J Mol Biol 353 (2005) 600-612. HX-MS is used to probe the solution behavior of ERK2 by monitoring AMP-PNP binding. Whereas active ERK2 forms interactions with nucleotide in both the N- and C-terminal lobes, inactive ERK2 shows significantly weaker C-terminal interactions. This suggests that ERK2 is constrained from adopting a closed conformation before activation.
34. Hoofnagle A.N., Resing K.A., Goldsmith E.J., and Ahn N.G. Changes in protein conformational mobility upon activation of extracellular regulated protein kinase-2 as detected by hydrogen exchange. Proc Natl Acad Sci USA 98 (2001) 956-961
35. Emrick MA, Lee T, Starkey PJ, Mumby MC, Resing KA, Ahn NG: The gatekeeper residue controls autoactivation of ERK2 via a pathway of intramolecular connectivity. Proc Natl Acad Sci USA 2006, in press. HX-MS analysis of ERK2 reveals involvement of the DFG motif in coupling the gatekeeper residue to the activation lip, through a series of sidechain and backbone connectivities.
36. d measurements confirm that R-subunit affinity is reduced in the mutant.
37. Wu J., Yang J., Kannan N., Madhusudan M., Xuong N.H., Ten Eyck L.F., and Taylor S.S. Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helix. Protein Sci 14 (2005) 2871-2879
38. Yang J., Ten Eyck L.F., Xuong N.H., and Taylor S.S. Crystal structure of a cAMP-dependent protein kinase mutant at 1.26 angstrom: new insights into the catalytic mechanism. J Mol Biol 336 (2004) 473-487
39. Anand G.S., Law D., Mandell J.G., Snead A.N., Tsigelny I., Taylor S.S., Ten Eyck L.F., and Komives E.A. Identification of the protein kinase A regulatory R-I alpha-catalytic subunit interface by amide H/2H exchange and protein docking. Proc Natl Acad Sci USA 100 (2003) 13264-13269
40. Kim C., Xuong N.H., and Taylor S.S. Crystal structure of a complex between the catalytic and regulatory (RI alpha) subunits of PKA. Science 307 (2005) 690-696. This landmark crystallographic study reveals details of the interactions between the catalytic and regulatory subunits of PKA, and dramatic conformational changes in the R-subunit upon binding.
41. Wong L., Jennings P.A., and Adams J.A. Communication pathways between the nucleotide pocket and distal regulatory sites in protein kinases. Acc Chem Res 37 (2004) 304-311
42. Cole P.A., Shen K., Qiao Y.F., and Wang D.X. Protein tyrosine kinases Src and Csk: a tail's tale. Curr Opin Chem Biol 7 (2003) 580-585
43. Takeuchi S., Takayama Y., Ogawa A., Tamura K., and Okada M. Transmembrane phosphoprotein Cbp positively regulates the activity of the carboxyl-terminal Src kinase. Csk. J Biol Chem 275 (2000) 29183-29186
44. Wong L., Lieser S.A., Miyashita O., Miller M., Tasken K., Onuchic J.N., Adams J.A., Woods V.L., and Jennings P.A. Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation. J Mol Biol 351 (2005) 131-143. HX-MS is used to probe the effects on Csk upon binding its allosteric activator, Cbp. Cbp binding not only affects the SH2 domain and SH2-kinase linker as expected, but also alters the exchange rate in the active site. The study shows that the allosteric activator can affect the active site dynamics or conformation, distal to the site of binding.
45. Ogawa A., Takayama Y., Sakai H., Chong K.T., Takeuchi S., Nakagawa A., Nada S., Okada M., and Tsukihara T. Structure of the carboxyl-terminal Src kinase, Csk. J Biol Chem 277 (2002) 14351-14354
46. Lin X.F., Wang Y.H., Ahmadibeni Y., Parang K., and Sun G.Q. Structural basis for domain-domain communication in a protein tyrosine kinase, the C-terminal Src kinase. J Mol Biol 357 (2006) 1263-1273
47. Mikkola E.T., and Bergman M. Conserved hydrophobicity in the SH2-kinase linker is required for catalytic activity of Csk and CHK. FEBS Lett 544 (2003) 11-14
48. Wong L., Lieser S., Chie-Leon B., Miyashita O., Aubol B., Shaffer J., Onuchic J.N., Jennings P.A., Woods V.L., and Adams J.A. Dynamic coupling between the SH2 domain and active site of the COOH terminal Src kinase, Csk. J Mol Biol 341 (2004) 93-106
49. Hamuro Y., Wong L., Shaffer J., Kim J.S., Stranz D.D., Jennings P.A., Woods V.L., and Adams J.A. Phosphorylation driven motions in the COOH-terminal Src kinase, Csk, revealed through enhanced hydrogen-deuterium exchange and mass spectrometry (DXMS). J Mol Biol 323 (2002) 871-881