Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization

Blood

Volumn 125, Issue 19, 2015, Pages 2995-3005

  Kosoff, Rachelle E ^a,b   Aslan, Joseph E ^c   Kostyak, John C ^d   Dulaimi, Essel ^a   Chow, Hoi Yee ^a   Prudnikova, Tatiana Y ^a   Radu, Maria ^a   Kunapuli, Satya P ^d   McCarty, Owen J T ^c   Chernoff, Jonathan ^a  

^a FOX CHASE CANCER CENTER   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c Oregon Health and Science University Department of Biomedical Engineering   (United States)

^d TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AURORA A KINASE; AURORA B KINASE; AURORA C KINASE; BETA TUBULIN; BETA1 TUBULIN; COFILIN; FIBRINOGEN RECEPTOR; LIM KINASE 1; P21 ACTIVATED KINASE 1; P21 ACTIVATED KINASE 2; P21 ACTIVATED KINASE 3; UNCLASSIFIED DRUG; PAX2 PROTEIN, MOUSE; TRANSCRIPTION FACTOR PAX2;

ADULT; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BONE MARROW; CYTOSKELETON; ENZYME PHOSPHORYLATION; HEMATOLOGICAL PARAMETERS; MEGAKARYOBLAST; MEGAKARYOCYTE; MEGAKARYOPOIESIS; MOUSE; NONHUMAN; POLYPLOIDY; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; THROMBOCYTE; THROMBOCYTOPENIA; THROMBOCYTOPOIESIS; ANIMAL; C57BL MOUSE; FLUORESCENCE MICROSCOPY; GENETICS; KNOCKOUT MOUSE; METABOLISM; MITOSIS; PATHOLOGY; PHYSIOLOGY; SCID MOUSE; STEM CELL;

ANIMALS; BLOOD PLATELETS; BONE MARROW; CYTOSKELETON; MEGAKARYOCYTES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, SCID; MICROSCOPY, FLUORESCENCE; MITOSIS; PAX2 TRANSCRIPTION FACTOR; POLYPLOIDY; STEM CELLS; THROMBOCYTOPENIA; THROMBOPOIESIS;

EID: 84983454132     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-10-604504     Document Type: Article

References (66)

1. Nakeff A, Maat B. Separation of megakaryocytes from mouse bone marrow by velocity sedimentation. Blood. 1974;43(4):591-595.
2. Avraham H. Regulation of megakaryocytopoiesis. Stem Cells. 1993;11(6):499-510.
3. Thon JN, Montalvo A, Patel-Hett S, et al. Cytoskeletal mechanics of proplatelet maturation and platelet release. J Cell Biol. 2010;191(4): 861-874.
4. Machlus KR, Italiano JE Jr. The incredible journey: From megakaryocyte development to platelet formation. J Cell Biol. 2013;201(6): 785-796.
5. Thon JN, Mazutis L, Wu S, et al. Platelet bioreactor-on-a-chip. Blood. 2014;124(12): 1857-1867.
6. de Sauvage FJ, Hass PE, Spencer SD, et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature. 1994; 369(6481):533-538.
7. Mazharian A, Watson SP, Severin S. Critical role for ERK1/2 in bone marrow and fetal liver-derived primary megakaryocyte differentiation, motility, and proplatelet formation. Exp Hematol. 2009; 37(10):1238-1249.
8. Rojnuckarin P, Drachman JG, Kaushansky K. Thrombopoietin-induced activation of the mitogen-activated protein kinase (MAPK) pathway in normal megakaryocytes: role in endomitosis. Blood. 1999;94(4):1273-1282.
9. Nakao T, Geddis AE, Fox NE, Kaushansky K. PI3K/Akt/FOXO3a pathway contributes to thrombopoietin-induced proliferation of primary megakaryocytes in vitro and in vivo via modulation of p27(Kip1). Cell Cycle. 2008;7(2):257-266.
10. Radu M, Semenova G, Kosoff R, Chernoff J. PAK signalling during the development and progression of cancer. Nat Rev Cancer. 2014; 14(1):13-25.
11. Coles LC, Shaw PE. PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during crosscascade activation of the ERK pathway. Oncogene. 2002;21(14):2236-2244.
12. 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(5):253-259.
13. Kosoff R, Chow HY, Radu M, Chernoff J. Pak2 kinase restrains mast cell FcϵRI receptor signaling through modulation of Rho protein guanine nucleotide exchange factor (GEF) activity. J Biol Chem. 2013;288(2):974-983.
14. Zhao ZS, Lim JP, Ng YW, Lim L, Manser E. The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A. Mol Cell. 2005;20(2):237-249.
15. Dorrance AM, De Vita S, Radu M, et al. The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment. Blood. 2013;121(13): 2474-2482.
16. Arai A, Jin A, Yan W, et al. SDF-1 synergistically enhances IL-3-induced activation of the Raf-1/ MEK/Erk signaling pathway through activation of Rac and its effector Pak kinases to promote hematopoiesis and chemotaxis. Cell Signal. 2005; 17(4):497-506.
17. Aslan JE, Baker SM, Loren CP, et al. The PAK system links Rho GTPase signaling to thrombinmediated platelet activation. Am J Physiol Cell Physiol. 2013;305(5):C519-C528.
18. Aslan JE, Itakura A, Haley KM, et al. p21 activated kinase signaling coordinates glycoprotein receptor VI-mediated platelet aggregation, lamellipodia formation, and aggregate stability under shear. Arterioscler Thromb Vasc Biol. 2013;33(7):1544-1551.
19. Crespin M, Vidal C, Picard F, Lacombe C, Fontenay M. Activation of PAK1/2 during the shedding of platelet microvesicles. Blood Coagul Fibrinolysis. 2009;20(1):63-70.
20. Suzuki-Inoue K, Yatomi Y, Asazuma N, et al. Rac, a small guanosine triphosphate-binding protein, and p21-activated kinase are activated during platelet spreading on collagen-coated surfaces: roles of integrin alpha(2)beta(1). Blood. 2001; 98(13):3708-3716.
21. Vidal C, Geny B, Melle J, Jandrot-Perrus M, Fontenay-Roupie M. Cdc42/Rac1-dependent activation of the p21-activated kinase (PAK) regulates human platelet lamellipodia spreading: implication of the cortical-actin binding protein cortactin. Blood. 2002;100(13):4462-4469.
22. Teo M, Manser E, Lim L. Identification and molecular cloning of a p21cdc42/rac1-activated serine/threonine kinase that is rapidly activated by thrombin in platelets. J Biol Chem. 1995;270(44): 26690-26697.
23. Akbar H, Kim J, Funk K, et al. Genetic and pharmacologic evidence that Rac1 GTPase is involved in regulation of platelet secretion and aggregation. J Thromb Haemost. 2007;5(8): 1747-1755.
24. Akbar H, Shang X, Perveen R, et al. Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation. PLoS ONE. 2011;6(7): e22117.
25. Pleines I, Dütting S, Cherpokova D, et al. Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42. Blood. 2013;122(18):3178-3187.
26. Menges CW, Sementino E, Talarchek J, et al. Group I p21-activated kinases (PAKs) promote tumor cell proliferation and survival through the AKT1 and Raf-MAPK pathways. Mol Cancer Res. 2012;10(9):1178-1188.
27. Deacon SW, Beeser A, Fukui JA, et al. An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase. Chem Biol. 2008;15(4):322-331.
28. Licciulli S, Maksimoska J, Zhou C, et al. FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem. 2013;288(40): 29105-29114.
29. Ong CC, Jubb AM, Jakubiak D, et al. P21-activated kinase 1 (PAK1) as a therapeutic target in BRAF wild-type melanoma. J Natl Cancer Inst. 2013;105(9):606-607.
30. Crawford JJ, Hoeflich KP, Rudolph J. p21-Activated kinase inhibitors: a patent review. Expert Opin Ther Pat. 2012;22(3):293-310.
31. Kühn R, Schwenk F, Aguet M, Rajewsky K. Inducible gene targeting in mice. Science. 1995; 269(5229):1427-1429.
32. Phee H, Au-Yeung BB, Pryshchep O, et al. Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation. eLife. 2014;3:e02270.
33. Chow HY, Dong B, Duron SG, et al. Group I Paks as therapeutic targets in NF2-deficient meningioma. Oncotarget. 2015;6(4):1981-1994.
34. Prislovsky A, Marathe B, Hosni A, et al. Rapid platelet turnover in WASP(-) mice correlates with increased ex vivo phagocytosis of opsonized WASP(-) platelets. Exp Hematol. 2008;36(5): 609-623.
35. Kostyak JC, Naik MU, Naik UP. Calciumand integrin-binding protein 1 regulates megakaryocyte ploidy, adhesion, and migration. Blood. 2012;119(3):838-846.
36. Pronk CJ, Rossi DJ, Månsson R, et al. Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy. Cell Stem Cell. 2007;1(4):428-442.
37. Allen JD, Jaffer ZM, Park SJ, et al. p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics. Blood. 2009;113(12):2695-2705.
38. Higuchi M, Onishi K, Kikuchi C, Gotoh Y. Scaffolding function of PAK in the PDK1-Akt pathway. Nat Cell Biol. 2008;10(11):1356-1364.
39. Staser K, Shew MA, Michels EG, et al. A Pak1-PP2A-ERM signaling axis mediates F-actin rearrangement and degranulation in mast cells. Exp Hematol. 2013;41(1):56-66.
40. Badolia R, Manne BK, Dangelmaier C, Chernoff J, Kunapuli SP. Gq-mediated Akt translocation to the membrane: a novel PIP3-independent mechanism in platelets. Blood. 2015;125(1): 175-184.
41. Lee LG, Chen CH, Chiu LA. Thiazole orange: a new dye for reticulocyte analysis. Cytometry. 1986;7(6):508-517.
42. Koh KR, Yamane T, Ohta K, Hino M, Takubo T, Tatsumi N. Pathophysiological significance of simultaneous measurement of reticulated platelets, large platelets and serum thrombopoietin in non-neoplastic thrombocytopenic disorders. Eur J Haematol. 1999;63(5):295-301.
43. Guthikonda S, Alviar CL, Vaduganathan M, et al. Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease. JAm Coll Cardiol. 2008;52(9):743-749.
44. Ebbe S. Biology of megakaryocytes. Prog Hemost Thromb. 1976;3:211-229.
45. Machlus KR, Thon JN, Italiano JE Jr. Interpreting the developmental dance of the megakaryocyte: a review of the cellular and molecular processes mediating platelet formation. Br J Haematol. 2014; 165(2):227-236.
46. Chow HY, Jubb AM, Koch JN, et al. p21-Activated kinase 1 is required for efficient tumor formation and progression in a Ras-mediated skin cancer model. Cancer Res. 2012;72(22):5966-5975.
47. Molli PR, Li DQ, Murray BW, Rayala SK, Kumar R. PAK signaling in oncogenesis. Oncogene. 2009;28(28):2545-2555.
48. Patel SR, Richardson JL, Schulze H, et al. Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes. Blood. 2005;106(13): 4076-4085.
49. Patel-Hett S, Richardson JL, Schulze H, et al. Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules. Blood. 2008;111(9): 4605-4616.
50. Tablin F, Castro M, Leven RM. Blood platelet formation in vitro. The role of the cytoskeleton in megakaryocyte fragmentation. J Cell Sci. 1990; 97(Pt 1):59-70.
51. Zhao ZS, Manser E. PAK family kinases: Physiological roles and regulation. Cell Logist. 2012;2(2):59-68.
52. Baatout S, Chatelain B, Staquet P, Symann M, Chatelain C. Inhibition of actin polymerization by cytochalasin B induces polyploidization and increases the number of nucleolar organizer regions in human megakaryocyte cell lines. Anticancer Res. 1998;18(1A):459-464.
53. Baatout S, Chatelain B, Staquet P, Symann M, Chatelain C. Inhibition of tubulin polymerization in megakaryocyte cell lines leads to polyploidization which affects the metabolism of actin. Anticancer Res. 1998;18(3A):1553-1561.
54. van der Loo B, Hong Y, Hancock V, Martin JF, Erusalimsky JD. Antimicrotubule agents induce polyploidization of human leukaemic cell lines with megakaryocytic features. Eur J Clin Invest. 1993; 23(10):621-629.
55. Ando Y, Yasuda S, Oceguera-Yanez F, Narumiya S. Inactivation of Rho GTPases with Clostridium difficile toxin B impairs centrosomal activation of Aurora-A in G2/M transition of HeLa cells. Mol Biol Cell. 2007;18(10):3752-3763.
56. Wen Q, Goldenson B, Silver SJ, et al. Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL. Cell. 2012;150(3):575-589.
57. Goldenson B, Kirsammer G, Stankiewicz MJ, Wen QJ, Crispino JD. Aurora kinase A is required for hematopoiesis, but is dispensable for murine megakaryocyte endomitosis and differentiation. Blood. 2015;(Feb):10.
58. Avanzi MP, Chen A, He W, Mitchell WB. Optimizing megakaryocyte polyploidization by targeting multiple pathways of cytokinesis. Transfusion. 2012;52(11):2406-2413.
59. Lordier L, Jalil A, Aurade F, et al. Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling. Blood. 2008;112(8):3164-3174.
60. Lordier L, Chang Y, Jalil A, et al. Aurora B is dispensable for megakaryocyte polyploidization, but contributes to the endomitotic process. Blood. 2010;116(13):2345-2355.
61. Geddis AE, Kaushansky K. Endomitotic megakaryocytes form a midzone in anaphase but have a deficiency in cleavage furrow formation. Cell Cycle. 2006;5(5):538-545.
62. Bender M, Eckly A, Hartwig JH, et al. ADF/ncofilin-dependent actin turnover determines platelet formation and sizing. Blood. 2010; 116(10):1767-1775.
63. Petrilli A, Copik A, Posadas M, et al. LIM domain kinases as potential therapeutic targets for neurofibromatosis type 2. Oncogene. 2014; 33(27):3571-3582.
64. Prudent R, Vassal-Stermann E, Nguyen CH, et al. Pharmacological inhibition of LIM kinase stabilizes microtubules and inhibits neoplastic growth. Cancer Res. 2012;72(17):4429-4439.
65. Zeng Y, Broxmeyer HE, Staser K, et al. Pak2 regulates hematopoietic progenitor cell proliferation, survival and differentiation. Stem Cells. 2015;(Jan):13.
66. Tiedt R, Schomber T, Hao-Shen H, Skoda RC. Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo. Blood. 2007;109(4):1503-1506.