p21-activated kinase 2 regulates endothelial development and function through the Bmk1/Erk5 pathway

Molecular and Cellular Biology

Volumn 35, Issue 23, 2015, Pages 3990-4005

  Radu, Maria ^a   Lyle, Karen ^b,c   Hoeflich, Klaus P ^b,d   Villamar Cruz, Olga ^a,e   Koeppen, Hartmut ^b   Chernoff, Jonathan ^a  

^a FOX CHASE CANCER CENTER   (United States)

^b GENENTECH INC   (United States)

^c Stemcentrx   (United States)

^d Blueprint Medicines   (United States)

^e UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

Author keywords

[No Author keywords available]

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE 7; P21 ACTIVATED KINASE 1; P21 ACTIVATED KINASE 2; P21 ACTIVATED KINASE;

ADULT; ANGIOGENESIS; ANIMAL CELL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BLOOD VESSEL PERMEABILITY; CELL ADHESION; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOSKELETON; EMBRYO; EMBRYO DEVELOPMENT; ENDOTHELIUM CELL; FEMALE; HUMAN; HUMAN CELL; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY MECHANISM; VASCULAR ENDOTHELIUM; YOLK SAC; ANIMAL; C57BL MOUSE; CAPILLARY PERMEABILITY; CARDIOVASCULAR MALFORMATION; CARDIOVASCULAR SYSTEM; CELL MOTION; CELL SURVIVAL; CYTOLOGY; EMBRYO DEATH; EMBRYOLOGY; ENDOTHELIUM; GENE DELETION; GENE EXPRESSION REGULATION; GENETICS; MAMMALIAN EMBRYO; METABOLISM; RNA INTERFERENCE; SIGNAL TRANSDUCTION; UMBILICAL VEIN ENDOTHELIAL CELL;

ANIMALS; CAPILLARY PERMEABILITY; CARDIOVASCULAR ABNORMALITIES; CARDIOVASCULAR SYSTEM; CELL MOVEMENT; CELL PROLIFERATION; CELL SURVIVAL; EMBRYO LOSS; EMBRYO, MAMMALIAN; ENDOTHELIUM; FEMALE; GENE DELETION; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; MALE; MICE, INBRED C57BL; MITOGEN-ACTIVATED PROTEIN KINASE 7; P21-ACTIVATED KINASES; RNA INTERFERENCE; SIGNAL TRANSDUCTION;

EID: 84946229511     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.00630-15     Document Type: Article

References (53)

1. Teo M, Manser E, Lim L. 1995. Identification and molecular cloning of a p21cdc42/rac1-activated serine/threonine kinase that is rapidly activated by thrombin in platelets. J Biol Chem 270:26690-26697. http://dx.doi.org/10.1074/jbc.270.44.26690.
2. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. 1994. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 367:40-46. http://dx.doi.org/10.1038/367040a0.
3. Arias-Romero LE, ChernoffJ. 2008. A tale of two Paks. Biol Cell 100:97-108. http://dx.doi.org/10.1042/BC20070109.
4. Stockton RA, Schaefer E, Schwartz MA. 2004. p21-activated kinase regulates endothelial permeability through modulation of contractility. J Biol Chem 279:46621-46630. http://dx.doi.org/10.1074/jbc. M408877200.
5. Liu J, Fraser SD, Faloon PW, Rollins EL, Vom Berg J, Starovic-Subota O, Laliberte AL, Chen JN, Serluca FC, Childs SJ. 2007. A betaPix Pak2a signaling pathway regulates cerebral vascular stability in zebrafish. Proc Natl Acad Sci U S A 104:13990-13995. http://dx.doi.org/10.1073/pnas.0700825104.
6. Koh W, Sachidanandam K, Stratman AN, Sacharidou A, Mayo AM, Murphy EA, Cheresh DA, Davis GE. 2009. Formation of endothelial lumens requires a coordinated PKCepsilon-, Src-, Pak- and Raf-kinasedependent signaling cascade downstream of Cdc42 activation. J Cell Sci 122:1812-1822. http://dx.doi.org/10.1242/jcs.045799.
7. Kiosses WB, Daniels RH, Otey C, Bokoch GM, Schwartz MA. 1999. A role for p21-activated kinase in endothelial cell migration. J Cell Biol 147:831-844. http://dx.doi.org/10.1083/jcb.147.4.831.
8. Kelly ML, Astsaturov A, ChernoffJ. 2013. Role of p21-activated kinases in cardiovascular development and function. Cell Mol Life Sci 70:4223-4228. http://dx.doi.org/10.1007/s00018-013-1347-8.
9. Galan Moya EM, Le Guelte A, Gavard J. 2009. PAKing up to the endothelium. Cell Signal 21:1727-1737. http://dx.doi.org/10.1016/j.cellsig.2009.08.006.
10. +/- mast cells. Blood 112:4646-4654. http://dx.doi.org/10.1182/blood-2008-04-155085.
11. Meng J, Meng Y, Hanna A, Janus C, Jia Z. 2005. Abnormal long-lasting synaptic plasticity and cognition in mice lacking the mental retardation gene Pak3. J Neurosci 25:6641-6650.
12. Hofmann C, Shepelev M, ChernoffJ. 2004. The genetics of Pak. J Cell Sci 117:4343-4354. http://dx.doi.org/10.1242/jcs.01392.
13. Wojciak-Stothard B, Tsang LY, Paleolog E, Hall SM, Haworth SG. 2006. Rac1 andRhoAas regulators of endothelial phenotypeand barrier function inhypoxia-induced neonatal pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 290:L1173-L1182. http://dx.doi.org/10.1152/ajplung.00309.2005.
14. Bagheri-Yarmand R, Vadlamudi RK, Wang RA, Mendelsohn J, Kumar R. 2000. Vascular endothelial growth factor up-regulation via p21-activated kinase-1 signaling regulates heregulin-beta1-mediated angiogenesis. J Biol Chem 275:39451-39457. http://dx.doi.org/10.1074/jbc. M006150200.
15. Gavard J, Gutkind JS. 2006. VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol 8:1223-1234. http://dx.doi.org/10.1038/ncb1486.
16. Lampugnani MG, Zanetti A, Breviario F, Balconi G, Orsenigo F, Corada M, Spagnuolo R, Betson M, Braga V, Dejana E. 2002. VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam. Mol Biol Cell 13:1175-1189. http://dx.doi.org/10.1091/mbc.01-07-0368.
17. Alva JA, Zovein AC, Monvoisin A, Murphy T, Salazar A, Harvey NL, Carmeliet P, Iruela-Arispe ML. 2006. VE-cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells. Dev Dyn 235:759-767. http://dx.doi.org/10.1002/dvdy.20643.
18. Voyta JC, Via DP, Butterfield CE, Zetter BR. 1984. Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein. J Cell Biol 99:2034-2040. http://dx.doi.org/10.1083/jcb.99.6.2034.
19. Nakatsu MN, Davis J, Hughes CC. 2007. Optimized fibrin gel bead assay for the study of angiogenesis. J Vis Exp 2007:186. http://dx.doi.org/10.3791/186.
20. Radu M, ChernoffJ. 2013. An in vivo assay to test blood vessel permeability. J Vis Exp 2013:e50062. http://dx.doi.org/10.3791/50062.
21. Stockton R, Reutershan J, Scott D, Sanders J, Ley K, Schwartz MA. 2007. Induction of vascular permeability: beta PIX and GIT1 scaffold the activation of extracellular signal-regulated kinase by PAK. Mol Biol Cell 18:2346-2355. http://dx.doi.org/10.1091/mbc. E06-07-0584.
22. Garvin S, Dabrosin C. 2003. Tamoxifen inhibits secretion of vascular endothelial growth factor in breast cancer in vivo. Cancer Res 63:8742-8748.
23. Risau W. 1997. Mechanisms of angiogenesis. Nature 386:671-674. http://dx.doi.org/10.1038/386671a0.
24. Koh W, Mahan RD, Davis GE. 2008. Cdc42-and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKCdependent signaling. J Cell Sci 121:989-1001. http://dx.doi.org/10.1242/jcs.020693.
25. Nehls V, Drenckhahn D. 1995. A novel, microcarrier-based in vitro assay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis. Microvasc Res 50:311-322. http://dx.doi.org/10.1006/mvre.1995.1061.
26. Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K. 1998. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature 393:809-812. http://dx.doi.org/10.1038/31735.
27. Nayal A, Webb DJ, Brown CM, Schaefer EM, Vicente-Manzanares M, Horwitz AR. 2006. Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics. J Cell Biol 173:587-589. http://dx.doi.org/10.1083/jcb.200509075.
28. Coniglio SJ, Zavarella S, Symons MH. 2008. Pak1 and Pak2 mediate tumor cell invasion through distinct signaling mechanisms. Mol Cell Biol 28:4162-4172. http://dx.doi.org/10.1128/MCB.01532-07.
29. Antonov AS, Lukashev ME, Romanov YA, Tkachuk VA, Repin VS, Smirnov VN. 1986. Morphological alterations in endothelial cells from human aorta and umbilical vein induced by forskolin and phorbol 12-myristate 13-acetate: a synergistic action of adenylate cyclase and protein kinase C activators. Proc Natl Acad Sci U S A 83:9704-9708. http://dx.doi.org/10.1073/pnas.83.24.9704.
30. Ong CC, Jubb AM, Zhou W, Haverty PM, Harris AL, Belvin M, Friedman LS, Koeppen H, Hoeflich KP. 2011. p21-activated kinase 1: PAK'ed with potential. Oncotarget 2:491-496. http://dx.doi.org/10.18632/oncotarget.271.
31. Hayashi M, Kim SW, Imanaka-Yoshida K, Yoshida T, Abel ED, Eliceiri B, Yang Y, Ulevitch RJ, Lee JD. 2004. Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure. J Clin Invest 113:1138-1148. http://dx.doi.org/10.1172/JCI200419890.
32. Nithianandarajah-Jones GN, Wilm B, Goldring CE, Muller J, Cross MJ. 2012. ERK5: structure, regulation and function. Cell Signal 24:2187-2196. http://dx.doi.org/10.1016/j.cellsig.2012.07.007.
33. Chow HY, Dong B, Duron SG, Campbell DA, Ong CC, Hoeflich KP, Chang LS, Welling DB, Yang ZJ, ChernoffJ. 2015. Group I Paks as therapeutic targets in NF2-deficient meningioma. Oncotarget 6:1981-1994. http://dx.doi.org/10.18632/oncotarget.2810.
34. Kiosses WB, Hood J, Yang S, Gerritsen ME, Cheresh DA, Alderson N, Schwartz MA. 2002. A dominant-negative p65 PAK peptide inhibits angiogenesis. Circ Res 90:697-702. http://dx.doi.org/10.1161/01.RES.0000014227.76102.5D.
35. Yurdagul A, Jr, Chen J, Funk SD, Albert P, Kevil CG, Orr AW. 2013. Altered nitric oxide production mediates matrix-specific PAK2 and NF-kappaB activation by flow. Mol Biol Cell 24:398-408. http://dx.doi.org/10.1091/mbc. E12-07-0513.
36. Dorrance AM, De Vita S, Radu M, Reddy PN, McGuinness MK, Harris CE, Mathieu R, Lane SW, KosoffR, Milsom MD, ChernoffJ, Williams DA. 2013. The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment. Blood 121:2474-2482. http://dx.doi.org/10.1182/blood-2012-10-460709.
37. KosoffR, Chow HY, Radu M, ChernoffJ. 2013. Pak2 kinase restrains mast cell FcepsilonRI receptor signaling through modulation of Rho protein guanine nucleotide exchange factor (GEF) activity. J Biol Chem 288:974-983. http://dx.doi.org/10.1074/jbc. M112.422295.
38. Arias-Romero LE, Villamar-Cruz O, Huang M, Hoeflich KP, ChernoffJ. 2013. Pak1 kinase links ErbB2 to beta-catenin in transformation of breast epithelial cells. Cancer Res 73:3671-3682. http://dx.doi.org/10.1158/0008-5472.CAN-12-4453.
39. Benitah SA, Frye M, Glogauer M, Watt FM. 2005. Stem cell depletion through epidermal deletion of Rac1. Science 309:933-935. http://dx.doi.org/10.1126/science.1113579.
40. Van den Broeke C, Radu M, Deruelle M, Nauwynck H, Hofmann C, Jaffer ZM, ChernoffJ, Favoreel HW. 2009. Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases. Proc Natl Acad Sci U S A 106:8707-8712. http://dx.doi.org/10.1073/pnas.0900436106.
41. Rudel T, Bokoch GM. 1997. Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science 276:1571-1574. http://dx.doi.org/10.1126/science.276.5318.1571.
42. Frank SR, Bell JH, Frodin M, Hansen SH. 2012. A betaPIX-PAK2 complex confers protection against Scrib-dependent and cadherin-mediated apoptosis. Curr Biol 22:1747-1754. http://dx.doi.org/10.1016/j.cub.2012.07.011.
43. Tan W, Palmby TR, Gavard J, Amornphimoltham P, Zheng Y, Gutkind JS. 2008. An essential role for Rac1 in endothelial cell function and vascular development. FASEB J 22:1829-1838. http://dx.doi.org/10.1096/fj.07-096438.
44. Srinivasan R, Zabuawala T, Huang H, Zhang J, Gulati P, Fernandez S, Karlo JC, Landreth GE, Leone G, Ostrowski MC. 2009. Erk1 and Erk2 regulate endothelial cell proliferation and migration during mouse embryonic angiogenesis. PLoS One 4:e8283. http://dx.doi.org/10.1371/journal.pone.0008283.
45. Wirth A, Schroeter M, Kock-Hauser C, Manser E, Chalovich JM, De Lanerolle P, Pfitzer G. 2003. Inhibition of contraction and myosin light chain phosphorylation in guinea-pig smooth muscle by p21-activated kinase 1. J Physiol 549:489-500. http://dx.doi.org/10.1113/jphysiol.2002.033167.
46. Reutershan J, Stockton R, Zarbock A, Sullivan GW, Chang D, Scott D, Schwartz MA, Ley K. 2007. Blocking p21-activated kinase reduces lipopolysaccharide-induced acute lung injury by preventing polymorphonuclear leukocyte infiltration. Am J Respir Crit Care Med 175:1027-1035. http://dx.doi.org/10.1164/rccm.200612-1822OC.
47. Birukova AA, Zagranichnaya T, Alekseeva E, Bokoch GM, Birukov KG. 2008. Epac/Rap and PKA are novel mechanisms of ANP-induced Rac-mediated pulmonary endothelial barrier protection. J Cell Physiol 215:715-724. http://dx.doi.org/10.1002/jcp.21354.
48. Buchner DA, Su F, Yamaoka JS, Kamei M, Shavit JA, Barthel LK, McGee B, Amigo JD, Kim S, Hanosh AW, Jagadeeswaran P, Goldman D, Lawson ND, Raymond PA, Weinstein BM, Ginsburg D, Lyons SE. 2007. pak2a mutations cause cerebral hemorrhage in redhead zebrafish. Proc Natl Acad Sci U S A 104:13996-14001. http://dx.doi.org/10.1073/pnas.0700947104.
49. Pi X, Garin G, Xie L, Zheng Q, Wei H, Abe J, Yan C, Berk BC. 2005. BMK1/ERK5 is a novel regulator of angiogenesis by destabilizing hypoxia inducible factor 1alpha. Circ Res 96:1145-1151. http://dx.doi.org/10.1161/01.RES.0000168802.43528.e1.
50. Sohn SJ, Sarvis BK, Cado D, Winoto A. 2002. ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive repressor of vascular endothelial growth factor expression. J Biol Chem 277:43344-43351. http://dx.doi.org/10.1074/jbc. M207573200.
51. Pi X, Yan C, Berk BC. 2004. Big mitogen-activated protein kinase (BMK1)/ERK5 protects endothelial cells from apoptosis. Circ Res 94:362-369. http://dx.doi.org/10.1161/01.RES.0000112406.27800.6F.
52. Rovida E, Navari N, Caligiuri A, Dello Sbarba P, Marra F. 2008. ERK5 differentially regulates PDGF-induced proliferation and migration of hepatic stellate cells. J Hepatol 48:107-115. http://dx.doi.org/10.1016/j.jhep.2007.08.010.
53. Komaravolu RK, Adam C, Moonen JR, Harmsen MC, Goebeler M, Schmidt M. 2015. Erk5 inhibits endothelial migration via KLF2-dependent downregulation of PAK1. Cardiovasc Res 105:86-95. http://dx.doi.org/10.1093/cvr/cvu236.