LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators

Medicinal Research Reviews

Volumn 32, Issue 5, 2012, Pages 968-998

  Manetti, Fabrizio ^a  

^a UNIVERSITY OF SIENA   (Italy)

Author keywords

Cofilin; Dual specificity kinases; LIM kinases; Protein protein interactions; Signaling pathway; Small molecule regulators

Indexed keywords

COFILIN; GUANOSINE TRIPHOSPHATASE; LIM KINASE; LIM KINASE 1; LIM KINASE 2; REGULATOR PROTEIN; RHO FACTOR; UNCLASSIFIED DRUG;

ARTICLE; CANCER INVASION; CELL CYCLE; CELL FUNCTION; CELL MIGRATION; CELLULAR DISTRIBUTION; DEVELOPMENTAL DISORDER; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYME SUBSTRATE; MACROMOLECULE; METASTASIS; NERVE CELL DIFFERENTIATION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; WILLIAMS BEUREN SYNDROME;

ANIMALS; DRUG DISCOVERY; HUMANS; LIM KINASES; MACROMOLECULAR SUBSTANCES; PHOSPHORYLATION; SMALL MOLECULE LIBRARIES; TRANSCRIPTION, GENETIC;

EID: 84864858844     PISSN: 01986325     EISSN: 10981128     Source Type: Journal    
DOI: 10.1002/med.20230     Document Type: Article

References (139)

1. Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T. Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif. Oncogene 1994;9:1605-1612.
2. Okano I, Hiraoka J, Otera H, Nunoue K, Ohashi K, Iwashita S, Hirai M, Mizuno K. Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs. J Biol Chem 1995;270:31321-31330.
3. Bach I. The LIM domain: Regulation by association. Mech Dev 2000;91:5-17.
4. Edwards DC, Gill GN. Structural features of LIM kinases that control effects on the actin cytoskeleton. J Biol Chem 1999;274:11352-11361.
5. Sumi T, Matsumoto K, Shibuya A, Nakamura T. Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase α. J Biol Chem 2001;276:23092-23096.
6. Toshima J, Ohashi K, Okano I, Nunoue K, Kishioka M, Kuma K, Miyata T, Hirai M, Baba T, Mizuno K. Identification and characterization of a novel protein kinase, TESK1, specifically expressed in testicular germ cells. J Biol Chem 1995;270:31331-31337.
7. Foletta VC, Moussi N, Sarmiere PD, Bamburg JR, Bernard O. LIM kinase 1, a key regulator of actin dynamics, is widely expressed in embryonic and adult tissues. Exp Cell Res 2004;294:392-405.
8. Acevedo K, Moussi N, Li R, Soo P, Bernard O. LIM kinase 2 is widely ecpressed in all tissues. J Histochem Cytochem 2006;54:487-501.
9. Salvarezza SB, Deborde S, Schreiner R, Campagne F, Kessels MM, Qualmann B, Caceres A, Kreitzer G, Rodriguez-Boulan E. LIM kinase 1 and cofilin regulate actin filament population required for dynamin-dependent apical carrier fission from the trans-Golgi network. Mol Biol Cell 2009;20:438-451.
10. Bernard O. Lim kinases, regulators of actin dynamics. Int J Biochem Cell Biol 2007;39:1071-1076.
11. Vlecken DH, Bagowski CP. LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells. Zebrafish 2009;6:433-439.
12. Tomiyoshi G, Horita Y, Nishita M, Ohashi K, Mizuno K. Caspase-mediated cleavage and activation of LIM-kinase 1 and its role in apoptotic membrane blebbing. Genes Cells 2004;9:591-600.
13. Hiraoka J, Okano I, Higuchi O, Yang N, Mizuno K. Self-association of LIM-kinase 1 mediated by the interaction between an N-terminal LIM domain and a C-terminal kinase domain. FEBS Lett 1996;399:117-121.
14. Li R, Soosairajah J, Harari D, Citri A, Price J, Ng HL, Morton CJ, Parker MW, Yarden Y, Bernard O. Hsp90 increases LIM kinase activity by promoting its homo-dimerization. FASEB J 2006;20:E417-E425.
15. Thirone ACP, Speight P, Zulys M, Rotstein OD, Szaszi K, Pedersen SF, Kapus A. Hyperosmotic stress induces Rho/Rho kinase/LIM kinase-mediated cofilin phosphorylation in tubular cells: Key role in the osmotically triggered F-actin response. Am J Physiol Cell Physiol 2009;296:C463-C475.
16. Abo A, Qu J, Cammarano MS, Dan C, Fritsch A, Baud V, Belisle B, Minden A. PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia. EMBO J 1998;17:6527-6540.
17. Edwards DC, Sanders LC, Bokoch GM, Gill GN. Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol 1999;1:253-259.
18. Delorme V, Machacek M, DerMardirossian C, Anderson KL, Wittmann T, Hanein D, Waterman-Storer C, Danuser G, Bokoch GM. Cofilin activity downstream of Pak1 regulates cell protrusion efficiency by organizing lamellipodium and lamella actin networks. Dev Cell 2007;13:646-662.
19. Misra UK, Deedwania R, Pizzo SV. Binding of activated α2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. J Biol Chem 2005;280:26278-26286.
20. Wu H, Zheng Y, Wang Z-X. Evaluation of the catalytic mechanism of the p21-activated protein kinase PAK2. Biochemistry 2003;42:1129-1139.
21. Dan C, Kelly A, Bernard O, Minden A. Cytoskeletal changes regulated by the Pak4 serine/threonine kinase are mediated by Lim kinase 1 and cofilin. J Biol Chem 2001;276:32115-32121.
22. Ahmed T, Shea K, Masters JRW, Jones GE, Wells CM. A PAK4-LIMK1 pathway drives prostate cancer cell migration downstream of HGF. Cell Signal 2008;20:1320-1328.
23. Wang W, Mouneimne G, Sidani M, Wyckoff J, Chen X, Makris A, Goswami S, Bresnick AR, Condeelis JS. The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors. J Cell Biol 2006;173:395-404.
24. Song X, Chen X, Yamaguchi H, Mouneimne G, Condeelis JS, Eddy RJ. Initiation of cofilin activity in response to EGF is uncoupled from cofilin phosphorylation and dephosphorylation in carcinoma cells. J Cell Sci 2006;119:2871-2881.
25. Jovceva E, Larsen MR, Waterfield MD, Baum B, Timms JF. Dynamic cofilin phosphorylation in the control of lamellipodial actin homeostasis. J Cell Sci 2007;120:1888-1897.
26. Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T. Control of actin reorganization by Slingshot, a family of phosphatases that deposphorylate ADF/cofilin. Cell 2002;108:233-246.
27. Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J 2005;24:473-486.
28. Nagata-Ohashi K, Ohta Y, Goto K, Chiba S, Mori R, Nishita M, Ohashi K, Kousaka K, Iwamatsu A, Niwa R, Uemura T, Mizuno K. A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia. J Cell Biol 2004;165:465-471.
29. Wang JY, Frenzel KE, Wen D, Falls DL. Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition. J Biol Chem 1998;273:20525-20534.
30. Birkenfeld J, Betz H, Roth D. Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3ζ. Biochem J 2003;369:45-54.
31. Li X, Ke Q, Li Y, Liu F, Zhu G, Li F. DGCR6L, a novel PAK4 interaction protein, regulates PAK4-mediated migration of human gastric cancer cell via LIMK1. Int J Biochem Cell Biol 2010;42:70-79.
32. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem 2000;275:3577-3582.
33. Sumi T, Matsumoto K, Nakamura T. Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase. J Biol Chem 2001;276:670-676.
34. Amano T, Tanabe K, Eto T, Narumuya S, Mizuno K. LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phosphorylation at threonine-505. Biochem J 2001;354:149-159.
35. Starinsky-Elbaz S, Faigenbloom L, Friedman E, Stein R, Kloog Y. The pre-GAP-related domain of neurofibromin regulates cell migration through the LIM kinase/cofilin pathway. Mol Cell Neurosci 2009;42:278-287.
36. Chen Q, Peto CA, Shelton GD, Mizisin A, Sawchenko PE, Schubert D. Loss of modifier of cell adhesion reveals a pathway leading to axonal degeneration. J Neurosci 2009;29:118-130.
37. Kobayashi M, Nishita M, Mishima T, Ohashi K, Mizuno K. MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration. EMBO J 2006;25:713-726.
38. Gong C, Stoletov KV, Terman BI. VEGF treatment induces signaling pathways that regulate both actin polymerization and depolymerization. Angiogenesis 2004;7:313-321.
39. Coé MC, Lavoie JR, Houle F, Poirier A, Rousseau S, Huot J. Regulation of vascular endothelial growth factor-induced endothelial cell migration by LIM kinase 1-mediated phosphorylation of annexin 1. J Biol Chem 2010;285:8013-8021.
40. Scott GA, McClelland LA, Fricke AF, Fender A. Plexin C1, a receptor for semaphorin 7a, inactivates cofilin and is a potential tumor suppressor for melanoma progression. J Invest Dermatol 2009;129:954-963.
41. Scott G. Tumor suppression through Plexin C1. WO2009155310 A1.
42. Lazova R, Gould Rothberg BE, Rimm D, Scott G. The semaphorin 7A receptor Plexin C1 is lost during melanoma metastasis. Am J Dermatopathol 2009;31:177-181.
43. Nadella KS, Saji M, Jacob NK, Pavel E, Ringel MD, Kirschner LS. Regulation of actin function by protein kinase A-mediated phosporylation of LIMK1. EMBO Rep 2009;10:599-605.
44. Howe AK, Juliano RL. Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase. Nat Cell Biol 2000;2:593-600.
45. Chen X, Macara IG. Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly. Cell Biol 2006;172:671-678.
46. Alahari SK, Lee JW, Juliano RL. Nischarin, a novel protein that interacts with the integrin α5 subunit and inhibits cell migration. J Cell Biol 2000;151:1141-1154.
47. Ding Y, Milosavljevic T, Alahari SK. Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell invasion. Mol Cell Biol 2008;28:3742-3756.
48. Suyama E, Wadhwa R, Kawasaki H, Yaguchi T, Kaul SC, Nakajima M, Taira K. LIM kinase-2 targeting as a possible anti-metastasis therapy. J Gene Med 2004;6:357-363.
49. Yoshioka K, Foletta V, Bernard O, Ito K. A role for LIM kinase in cancer invasion. Proc Natl Acad Sci USA 2003;100:7247-7252.
50. Yang X, Yu K, Hao Y, Li DM, Stewart R, Insogna KL, Xu T. LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nat Cell Biol 2004;6:609-617.
51. Hirota T, Morisaki T, Nishiyama Y, Marumoto T, Tada K, Hara T, Masuko N, Inagaki M, Hatakeyama K, Saya H. Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor. J Cell Biol 2000;149:1073-1086.
52. Amano T, Kaji N, Ohashi K, Mizuno K. Mitosis-specific activation of LIM motif-containing protein kinase and roles of cofilin phosphorylation and dephosphorylation in mitosis. J Biol Chem 2002;277:22093-22102.
53. Ross JS. DNA ploidy and cell cycle analysis in cancer diagnosis and prognosis. Oncology (Williston Park) 1996;10:867-890.
54. Fields S, Song O. A novel genetic system to detect protein-protein interactions. Nature 1989;340:245-246.
55. Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier J-M. Functional proteomics mapping of a human signaling pathway. Genome Res 2004;14:1324-1332.
56. Foletta VC, Lim MA, Soosairajah J, Kelly AP, Stanley EG, Shannon M, He W, Das S, Massague J, Bernard O. Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. J Cell Biol 2003;162:1089-1098.
57. Lee-Hoeflich ST, Causing CG, Podkowa M, Zhao X, Wrana JL, Attisano L. Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP-dependent dendritogenesis. EMBO J 2004;23:4792-4801.
58. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Philips JA III, Newman J, Williams D, Galie N, Manes A, McNeil K, Yacoub M, Mikhail G, Rogers P, Corris P, Humbert M, Donnai D, Martensson G, Tranebjaerg L, Loyd JE, Trembath RC, Nichols WC. BMPRII haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 2001;68:92-102.
59. Hocking JC, Hehr CL, Bertolesi G, Funakoshi H, Nakamura T, McFarlane S. LIMK1 acts downstream of BMP signaling in developing retinal ganglion cell axons but not dendrites. Dev Biol 2009;330:273-285.
60. Scott RW, Olson MF. LIM kinases: Function, regulation and association with human disease. J Mol Med 2007;85:555-568.
61. Zoudilova M, Kumar P, Ge L, Wang P, Bokoch GM, DeFea KA β-Arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2. J Biol Chem 2007;282:20634-20646.
62. Gohla A, Birkenfeld J, Bokoch GM. Chronophin, a novel had-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat Cell Biol 2005;7:21-29.
63. Wiggan O, Bernstein BW, Bamburg JR. A phosphatase for cofilin to be had. Nat Cell Biol 2005;7:8-9.
64. Huang TY, DerMardirossian C, Bokoch GM. Cofilin phosphatases and regulation of actin dynamics. Curr Opin Cell Biol 2006;18:26-31.
65. Pandey D, Goyal P, Bamburg JR, Siess W. Regulation of LIM-kinase and cofilin in thrombin-stimulated platelets. Blood 2006;107:575-583.
66. Goyal P, Pandey D, Behring A, Siess W. Inhibition of nuclear import of LIMK2 in endothelial cells by protein kinase C-dependent phosphorylation at Ser-283. J Biol Chem 2005;280:27569-27577.
67. Goyal P, Pandey D, Siess W. Phosphorylation-dependent regulation of unique nuclear and nucleolar localization signals of LIM kinase 2 in endothelial cells. J Biol Chem 2006;281:25223-25230.
68. Sacchetti P, Carpentier R, Segard P, Olive-Cren C, Lefebvre P. Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1. Nucleic Acids Res 2006;34:5515-5527.
69. Joseph B, Wallen-Mackenzie A, Benoit G, Murata T, Joodmardi E, Okret S, Perlmann T. p57(Kip2) cooperates with Nurr1 in developing dopamine cells. Proc Natl Acad Sci USA 2003;100:15619-15624.
70. Kremer D, Heinen A, Jadasz J, Göttle P, Zimmermann K, Zickler P, Jander S, Hartung HP, Küry P. p57kip2 Is dynamically regulated in experimental autoimmune encephalomyelitis and interferes with oligodendroglial maturation. Proc Natl Acad Sci USA 2009;106:9087-9092.
71. Vlachos P, Joseph B. The Cdk inhibitor p57(Kip2) controls LIM-kinase 1 activity and regulates actin cytoskeleton dynamics. Oncogene 2009;28:4175-4188.
72. Yokoo T, Toyoshima H, Miura M, Wang Y, Iida KT, Suzuki H, Sone H, Shimano H, Gotoda T, Nishimori S, Tanaka K, Yamada N. p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus. J Biol Chem 2003;278:52919-52923.
73. Yang EJ, Yoon J-H, Min DS, Chung KC. LIM kinase 1 activates cAMP-responsive element-binding protein during the neuronal differentiation of immortalized hippocampal progenitor cells. J Biol Chem 2004;279:8903-8910.
74. Lopatina NG, Zachepilo TG, Savvateeva-Popova EV. LIM kinase-1 in the cerebral ganglion of Drosophila with genetic disturbances of kynurenine balance. Doklady Biol Sci 2008;418:1-3.
75. Nishita M, Tomizawa C, Yamamoto M, Horita Y, Ohashi K, Mizuno K. Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. J Cell Biol 2005;171:349-359.
76. San Martin A, Lee MY, Williams HC, Mizuno K, Lassegue B, Griendling KK. Dual regulation of cofilin activity by LIM kinase and slingshot-1L phosphatase controls plateled-derived growth factor-induced migration of human aortic smooth muscle cells. Circ Res 2008;102:432-438.
77. Bagheri-Yarmand R, Mazumdar A, Sahin AA, Kumar R. Lim kinase 1 increases tumor metastasis of human breast cancer cells via regulation of the urokinase-type plasminogen activator system. Int J Cancer 2006;118:2703-2710.
78. Nishita M, Aizawa H, Mizuno K. Stromal cell-derived factor 1α activates LIM kinase 1 and induces cofilin phosphorylation for T-cell chemotaxis. Mol Cell Biol 2002;22:774-783.
79. Azab AK, Azab F, Blotta S, Pitsillides CM, Thompson B, Runnels JM, Roccaro AM, Ngo HT, Melhem MR, Sacco A, Jia X, Anderson KC, Lin CP, Rollins BJ, Ghobrial IM. RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood 2009;114:619-629.
80. Sun R, Gao P, Chen L, Ma D, Wang J, Oppenheim JJ, Zhang N. Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis of human brest cancer cells. Cancer Res 2005;65:1433-1441.
81. Guo H, Gu F, Li W, Zhan B, Niu R, Fu L, Zhang N, Ma Y. Reduction of protein kinase C ζ inhibits migration and invasion of human glioblastoma cells. J Neurochem 2009;109:203-213.
82. Liu Y, Wang B, Wang J, Wan W, Sun R, Zhao Y, Zhang N. Down-regulation of PKCzeta expression inhibits chemotaxis signal transduction in human lung cancer cells. Lung Cancer 2008;63:210-218.
83. Zhang B, Ma Y, Guo H, Sun B, Niu R, Ying G, Zhang N. Akt2 is required for macrophage chemotaxis. Eur J Immunol 2009;39:894-901.
84. Wang J, Wan S, Sun R, Liu Y, Sun X, Ma D, Zhang N. Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells. Cell Signal 2008;20:1025-1034.
85. Guo H, Ma Y, Zhang B, Sun B, Niu R, Ying G, Zhang N. Pivotal advance: PKCζ is required for migration of macrophages. J Leukoc Biol 2009;85:911-918.
86. Sumi T, Hashigasako A, Matsumoti K, Nakamura T. Different activity regulation and subcellular localization of LIMK1 and LIMK2 during cell cycle transition. Exp Cell Res 2006;312:1021-1030.
87. Sumi T, Matsumoto K, Nakamura T. Mitosis-dependent phosphorylation and activation of lim-kinase 1. Biochem Biophys Res Commun 2002;290:1315-1320.
88. Kaji N, Muramoto A, Mizuno K. LIM kinase-mediated cofilin phosphorylation during mitosis is required for precise spindle positioning. J Biol Chem 2008;283:4983-4992.
89. Chakrabarti R, Jones JL, Oelschlager DK, Tapia T, Tousson A, Grizzle WE. Phosphorylated LIM kinases colocalize with γ-tubulin in centrosomes during early stages of mitosis. Cell Cycle 2007;6:2944-2952.
90. Wang Y, Shibasaki F, Mizuno K. Calcium signal-induced cofilin dephosphorylation is mediated by slingshot via calcineurin. J Biol Chem 2005;280:12683-12689.
91. Aizawa H, Wakatsuki S, Ishii A, Moriyama K, Sasaki Y, Ohashi K, Sekine-Aizawa Y, Sehara-Fujisawa A, Mizuno K, Goshima Y, Yahara I. Phosphorylation of cofilin by lim-kinase is necessary for semaphorin 3a-induced growth cone collapse. Nat Neurosci 2001;4:367-373.
92. Tursun B, Schluter A, Peters MA, Viehweger B, Ostendorff HP, Soosairajah J, Drung A, Bossenz M, Johnsen SA, Schweizer M, Bernard O, Bach I. The ubiquitin ligase rnf6 regulates local LIM kinase 1 levels in axonal growth cones. Genes Dev 2005;19:2307-2319.
93. Lim MK, Kawamura T, Ohsawa Y, Ohtsubo M, Asakawa S, Takayanagi A, Shimizu N. Parkin interacts with LIM kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination. Exp Cell Res 2007;313:2858-2874.
94. Hsieh SH-K, Ferraro GB, Fournier AE. Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal inhibition through LIM kinase and slingshot phosphatase. J Neurosci 2006;26:1006-1015.
95. Montani L, Gerrits B, Gehrig P, Kempf A, Dimou L, Wollscheid B, Schwab ME. Neuronal Nogo-A modulates growth cone motility via Rho-GTP/LIMK1/cofilin in the unlesioned adult nervous system. J Biol Chem 2009;284:10793-10807.
96. Coolen M, Bally-Cuif L. MicroRNAs in brain development and physiology. Curr Opin Neurobiol 2009;19:461-470.
97. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME. A brain-specific microRNA regulates dendritic spine development. Nature 2006;439:283-289.
98. Yoong LF, Wan G, Too H-P. GDNF-induced cell signaling and neurite outgrowths are differentially mediated by GFRalpha1 isoforms. Mol Cell Neurosci 2009;41:464-473.
99. 2+/calmodulin-dependent protein kinase IV-mediated LIM-kinase activation is critical for calcium signal-induced neurite outgrowth. J Biol Chem 2009;284:28554-28562.
100. Honma M, Aznar Benitah S, Watt FM. Role of LIM kinases in normal and psoriatic human epidermis. Mol Biol Cell 2006;17:1888-1896.
101. Davila M, Frost AR, Grizzle WE, Chakrabarti R. LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: Implications in prostate cancer. J Biol Chem 2003;278:36868-36875.
102. Nishimura Y, Yoshioka K, Bernard O, Bereczky B, Itoh K. A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. Histochem Cell Biol 2006;126:627-638.
103. Okamoto I, Pirker C, Bilban M, Berger W, Losert D, Marosi C, Haas OA, Wolff K, Pehamberger H. Seven novel and stable translocations associated with oncogenic gene expression in malignant melanoma. Neoplasia 2005;7:303-311.
104. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W. Chemokine receptor cxcr4 downregulated by von hippel-lindau tumour suppressor pvhl. Nature 2003;425:307-311.
105. Sayi A. Functional analysis of the LIM kinase 1 and its role in cell cycle progression, PhD Thesis, University of Basel, Faculty of Science, 2008.
106. Mishima T, Naotsuka M, Horita Y, Sato M, Ohashi K, Mizuno K. LIM-kinase is critical for the mesenchymal-to-amoeboid cell morphological transition in 3D matrices. Biochem Biophys Res Commun 2010;392:577-581.
107. Shea KF, Wells CM, Garner AP, Jones GE. ROCK1 and LIMK2 interact in spread but not in blebbing cancer cells. PLoS One 2008;3:e3398.
108. Higuchi O, Amano T, Yang N, Mizuno K. Inhibition of activated Ras-induced neuronal differentiation of PC12 cells by the LIM domain of LIM-kinase 1. Oncogene 1997;14:1819-1825.
109. Smith AD, Gilchrist ID, Hood B, Tassabehji M, Karmiloff-Smith A. Inefficient search of large-scale space in Williams syndrome: Further insights on the role of LIMK1 deletion in deficits of spatial cognition. Perception 2009;38:694-701.
110. Heredia L, Helguera P, de Olmos S, Kedikian G, Sola Vigo F, LaFerla F, Staufenbiel M, de Olmos J, Busciglio J, Caceres A, Lorenzo, A. Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid β-induced degeneration: A potential mechanism of neuronal dystrophy in Alzheimer's disease. J Neurosci 2006;26:6533-6542.
111. Yamada Y, Metoki N, Yoshida H, Satoh K, Kato K, Hibino T, Yokoi K, Watanabe S, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y. Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals. Stroke 2008;39:2211-2218.
112. Akagawa H, Tajima A, Sakamoto Y, Krischek B, Yoneyama T, Kasuya H, Onda H, Hori T, Kubota M, Machida T, Saeki N, Hata A, Hashiguchi K, Kimura E, Kim CJ, Yang TK, Lee JY, Kimm K, Inoue I. A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms. Hum Mol Genet 2006;15:1722-1734.
113. Akagawa H, Narita A, Yamada H, Tajima A, Krischek B, Kasuya H, Hori T, Kubota M, Saeki N, Hata A, Mizutani T, Inoue I. Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptibility gene to intracranial aneurysms. Hum Genet 2007;121:377-387.
114. Kuzmin A, Jarvi K, Lo K, Spencer L, Chow GY, Macleod G, Wang Q, Varmuza S. Identification of potentially damaging amino acid substitutions leading to human male infertility. Biol Reprod 2009;81:319-326.
115. Wrobelski ST, Lin S, Leftheris K, He L, Seitz SP, Lin T-A, Vaccaro W. Phenyl-substituted pyrimidine compounds useful as kinase inhibitors. WO 2006/084017 A2.
116. Ross-Macdonald P, de Silva H, Guo Q, Xiao H, Hung C-Y, Penhallow B, Markwalder J, He L, Attar RM, Lin T, Seitz S, Tilford C, Wardwell-Swanson J, Jackson D. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther 2008;7:3490-3498.
117. Pouha ST, Shum MS, Goebel A, Bernard O, Kavallaris M. LIM-kinase 2, a regulator of actin dynamics, is involved in mitotic spindle integrity and sensitivity to microtubule-destabilizing drugs. Oncogene 2010;29:597-607.
118. Gorovoy M, Niu J, Bernard O, Profirovic J, Minshall R, Neamu R, Voyno-Yasenetskaya T. Lim kinase 1 coordinates microtubule stability and actin polymerization in human endothelial cells. J Biol Chem 2005;280:26533-26542.
119. Acevedo C, Li R, Soo P, Suryadinata R, Sarcevic B, Valova VA, Graham ME, Robinson PJ, Bernard O. The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules. Exp Cell Res 2007;313:4091-4106.
120. Harrison BA, Kimball SD, Mabon R, Rawlins DB, Rice DS, Voronkov MV, Zhang Y. Kinase inhibitors, compositions comprising them, and methods of their use. WO 2009/021169 A2.
121. Burgoon HA, Goodwin NC, Harrison BA, Healy JP, Liu Y, Mabon R, Marinelli B, Rawlins DB, Rice DS, Whitlock NA. LIMK inhibitors, compositions comprising them, and methods of their use. WO 2009/131940 A1.
122. Harrison BA, Whitlock NA, Voronkov MV, Almstead ZY, Gu K, Mabon R, Gardyan M, Hamman BD, Allen J, Gopinathan S, McKnight B, Crist M, Zhang Y, Liu Y, Courtney LF, Key B, Zhou J, Patel N, Yates PW, Liu Q, Wilson AGE, Kimball SD, Crosson CE, Rice DS, Rawlins DB. Novel class of LIM-kinase 2 inhibitors for the treatment of ocular hypertension and associated glaucoma. J Med Chem 2009;52:6515-6518.
123. Crosson CE, Sloan CF, Yates PW. Modulation of conventional outflow facility by the adenosine A1 agonist N6-cyclohexyladenosine. Invest Ophthalmol Vis Sci 2005;46:3795-3799.
124. Hizaki H, Ishida N, Matsugi T, Hara H. Remedy for glaucoma containing LIM kinase inhibitory compound as active ingredient. WO 2004/047868.
125. Gorovoy M, Koga T, Shen X, Jia Z, Yue BY, Voyno-Yasenetskaya T. Downregulation of LIM kinase 1 suppresses ocular inflammation and fibrosis. Mol Vis 2008;14:1951-1959.
126. Vardouli L, Moustakas A, Stournaras C. LIM-kinase 2 and cofilin phosphorylation mediate actin cytoskeleton reorganization induced by transforming growth factor-beta. J Biol Chem 2005;280:11448-11457.
127. Cordeiro MF. Role of transforming growth factor a in conjunctival scarring. Clin Sci (Lond) 2003;104:181-187.
128. Cordeiro MF. Beyond mitomycin: TGF-β and wound healing. Prog Retin Eye Res 2002;21:75-89.
129. Rueck A, Leeuw T, Herrmann M, Sibenhorn G. Use of LIMK-1, its analogues and ligands for the production of a medicament againts a thrombus formation or blood clotting disease. WO 2005/053734 A1.
130. Panitch A, Seal B. Kinases inhibitors and uses thereof. WO 2009/021137 A2.
131. Chen YT, Luo J, Feng Y. Discovery of LIM kinase-1 inhibitors. Abstracts of Papers, 239th ACS National Meeting, San Francisco, CA, 21-25 March 2010.
132. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The protein data bank. Nucleic Acids Res 2000;28:235-242.
133. Caporuscio F, Tafi A, González E, Manetti F, Esté JA, Botta M. A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120-CD4 protein-protein interactions. Bioorg Med Chem Lett 2009;19:6087-6091.
134. Grohmann D, Corradi V, Elbasyouny M, Baude A, Horenkamp F, Laufer SD, Manetti F, Botta M, Restle T. Small molecule inhibitors targeting HIV-1 reverse transcriptase dimerization. Chembiochem 2008;9:916-922.
135. Tintori C, Corradi V, Magnani M, Manetti F, Botta M. Targets looking for drugs: A multistep computational protocol for the development of structure-based pharmacophores and their applications for hit discovery. J Chem Inf Model 2008;48:2166-2179.
136. Mori M, Dietrich U, Manetti F, Botta M. Molecular dynamics and DFT study on HIV-1 nucleocapsid protein-7 in complex with viral genome. J Chem Inf Model 2010;50:638-650.
137. Olla S, Manetti F, Crespan E, Maga G, Angelucci A, Schenone S, Bologna M, Botta M. Indolyl-pyrrolone as a new scaffold for Pim1 inhibitors. Bioorg Med Chem Lett 2009;19:1512-1516.
138. Maga G, Falchi F, Garbelli A, Belfiore A, Witvrouw M, Manetti F, Botta M. Pharmacophore modeling and molecular docking led to the discovery of inhibitors of human immunodeficiency virus-1 replication targeting the human cellular aspartic acid-glutamic acid-alanine-aspartic acid box polypeptide 3. J Med Chem 2008;51:6635-6638.
139. Manetti F, Brullo C, Magnani M, Mosci F, Chelli B, Crespan E, Schenone S, Naldini A, Bruno O, Trincavelli ML, Maga G, Carraro F, Martini C, Bondavalli F, Botta M. Structure-based optimization of pyrazolo[3, 4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines. J Med Chem 2008;51:1252-1259.