PTEN negatively regulates engulfment of apoptotic cells by modulating activation of Rac GTPase

Journal of Immunology

Volumn 187, Issue 11, 2011, Pages 5783-5794

  Mondal, Subhanjan ^a,b   Ghosh Roy, Saurabh ^a,b   Loison, Fabien ^a,b   Li, Yitang ^a,b   Jia, Yonghui ^a,b   Harris, Chad ^b,c   Williams, David A ^b,c   Luo, Hongbo R ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

F ACTIN; GLYCOGEN SYNTHASE KINASE 3BETA; GUANINE NUCLEOTIDE EXCHANGE FACTOR; INTERLEUKIN 10; INTERLEUKIN 6; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RAC PROTEIN; RAC1 PROTEIN; RAC2 PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VAV1 PROTEIN;

ACTIN POLYMERIZATION; ANIMAL CELL; APOPTOSIS; ARTICLE; CELL TRANSPORT; CONTROLLED STUDY; CYTOKINE PRODUCTION; EFFEROCYTOSIS; ENZYME ACTIVATION; IN VITRO STUDY; IN VIVO STUDY; MOUSE; MYRISTYLATION; NONHUMAN; PERITONEUM MACROPHAGE; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION;

ANIMALS; APOPTOSIS; ENZYME ACTIVATION; MACROPHAGES; MICE; MICE, KNOCKOUT; PHAGOCYTOSIS; PTEN PHOSPHOHYDROLASE; RAC GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION;

EID: 82755190064     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1100484     Document Type: Article

References (63)

1. Ravichandran, K. S., and U. Lorenz. 2007. Engulfment of apoptotic cells: signals for a good meal. Nat. Rev. Immunol. 7: 964-974. (Pubitemid 350166061)
2. Elliott, M. R., F. B. Chekeni, P. C. Trampont, E. R. Lazarowski, A. Kadl, S. F. Walk, D. Park, R. I. Woodson, M. Ostankovich, P. Sharma, et al. 2009. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461: 282-286.
3. Lauber, K., E. Bohn, S. M. Kröber, Y. J. Xiao, S. G. Blumenthal, R. K. Lindemann, P. Marini, C. Wiedig, A. Zobywalski, S. Baksh, et al. 2003. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113: 717-730. (Pubitemid 36724936)
4. Fadok, V. A., D. R. Voelker, P. A. Campbell, J. J. Cohen, D. L. Bratton, and P. M. Henson. 1992. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148: 2207-2216.
5. Miyanishi, M., K. Tada, M. Koike, Y. Uchiyama, T. Kitamura, and S. Nagata. 2007. Identification of Tim4 as a phosphatidylserine receptor. Nature 450: 435-439. (Pubitemid 350126753)
6. Kobayashi, N., P. Karisola, V. Peña-Cruz, D. M. Dorfman, M. Jinushi, S. E. Umetsu, M. J. Butte, H. Nagumo, I. Chernova, B. Zhu, et al. 2007. TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 27: 927-940. (Pubitemid 50014866)
7. Park, D., A. C. Tosello-Trampont, M. R. Elliott, M. Lu, L. B. Haney, Z. Ma, A. L. Klibanov, J. W. Mandell, and K. S. Ravichandran. 2007. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450: 430-434. (Pubitemid 350126756)
8. Park, S. Y., M. Y. Jung, H. J. Kim, S. J. Lee, S. Y. Kim, B. H. Lee, T. H. Kwon, R. W. Park, and I. S. Kim. 2008. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ. 15: 192-201.
9. Akakura, S., S. Singh, M. Spataro, R. Akakura, J. I. Kim, M. L. Albert, and R. B. Birge. 2004. The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells. Exp. Cell Res. 292: 403-416. (Pubitemid 38018855)
10. Hanayama, R., M. Tanaka, K. Miwa, A. Shinohara, A. Iwamatsu, and S. Nagata. 2002. Identification of a factor that links apoptotic cells to phagocytes. Nature 417: 182-187. (Pubitemid 34506799)
11. Hanayama, R., M. Tanaka, K. Miyasaka, K. Aozasa, M. Koike, Y. Uchiyama, and S. Nagata. 2004. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304: 1147-1150. (Pubitemid 38661849)
12. Scott, R. S., E. J. McMahon, S. M. Pop, E. A. Reap, R. Caricchio, P. L. Cohen, H. S. Earp, and G. K. Matsushima. 2001. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411: 207-211. (Pubitemid 32455181)
13. Kinchen, J. M., J. Cabello, D. Klingele, K. Wong, R. Feichtinger, H. Schnabel, R. Schnabel, and M. O. Hengartner. 2005. Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans. Nature 434: 93-99. (Pubitemid 40349391)
14. Fadok, V. A., D. L. Bratton, A. Konowal, P. W. Freed, J. Y. Westcott, and P. M. Henson. 1998. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J. Clin. Invest. 101: 890-898. (Pubitemid 28096086)
15. Borregaard, N. 2010. Neutrophils, from marrow to microbes. Immunity 33: 657-670.
16. Elliott, M. R., S. Zheng, D. Park, R. I. Woodson, M. A. Reardon, I. J. Juncadella, J. M. Kinchen, J. Zhang, J. J. Lysiak, and K. S. Ravichandran. 2010. Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature 467: 333-337.
17. Jarzynka, M. J., B. Hu, K. M. Hui, I. Bar-Joseph, W. Gu, T. Hirose, L. B. Haney, K. S. Ravichandran, R. Nishikawa, and S. Y. Cheng. 2007. ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion. Cancer Res. 67: 7203-7211. (Pubitemid 47206548)
18. Gumienny, T. L., E. Brugnera, A. C. Tosello-Trampont, J. M. Kinchen, L. B. Haney, K. Nishiwaki, S. F. Walk, M. E. Nemergut, I. G. Macara, R. Francis, et al. 2001. CED-12/ELMO, a novel member of the CrkII/Dock180/ Rac pathway, is required for phagocytosis and cell migration. Cell 107: 27-41. (Pubitemid 32972035)
19. Camps, M., T. Rückle, H. Ji, V. Ardissone, F. Rintelen, J. Shaw, C. Ferrandi, C. Chabert, C. Gillieron, B. Françon, et al. 2005. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat. Med. 11: 936-943. (Pubitemid 41294438)
20. Smith, D. F., T. L. Deem, A. C. Bruce, J. Reutershan, D. Wu, and K. Ley. 2006. Leukocyte phosphoinositide-3 kinase gamma is required for chemokine-induced, sustained adhesion under flow in vivo. J. Leukoc. Biol. 80: 1491-1499. (Pubitemid 44904988)
21. Liu, L., K. D. Puri, J. M. Penninger, and P. Kubes. 2007. Leukocyte PI3Kgamma and PI3Kdelta have temporally distinct roles for leukocyte recruitment in vivo. Blood 110: 1191-1198. (Pubitemid 47281416)
22. Puri, K. D., T. A. Doggett, J. Douangpanya, Y. Hou, W. T. Tino, T. Wilson, T. Graf, E. Clayton, M. Turner, J. S. Hayflick, and T. G. Diacovo. 2004. Mechanisms and implications of phosphoinositide 3-kinase delta in promoting neutrophil trafficking into inflamed tissue. Blood 103: 3448-3456. (Pubitemid 38525677)
23. Puri, K. D., T. A. Doggett, C. Y. Huang, J. Douangpanya, J. S. Hayflick, M. Turner, J. Penninger, and T. G. Diacovo. 2005. The role of endothelial PI3Kgamma activity in neutrophil trafficking. Blood 106: 150-157. (Pubitemid 40967187)
24. Heit, B., L. Liu, P. Colarusso, K. D. Puri, and P. Kubes. 2008. PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP. J. Cell Sci. 121: 205-214. (Pubitemid 351228453)
25. Sasaki, T., J. Irie-Sasaki, R. G. Jones, A. J. Oliveira-dos-Santos, W. L. Stanford, B. Bolon, A. Wakeham, A. Itie, D. Bouchard, I. Kozieradzki, et al. 2000. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science 287: 1040-1046.
26. Hirsch, E., V. L. Katanaev, C. Garlanda, O. Azzolino, L. Pirola, L. Silengo, S. Sozzani, A. Mantovani, F. Altruda, and M. P. Wymann. 2000. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287: 1049-1053.
27. Liliental, J., S. Y. Moon, R. Lesche, R. Mamillapalli, D. Li, Y. Zheng, H. Sun, and H. Wu. 2000. Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases. Curr. Biol. 10: 401-404. (Pubitemid 30213387)
28. Gao, P., R. L. Wange, N. Zhang, J. J. Oppenheim, and O. M. Howard. 2005. Negative regulation of CXCR4-mediated chemotaxis by the lipid phosphatase activity of tumor suppressor PTEN. Blood 106: 2619-2626. (Pubitemid 41510732)
29. Kwak, Y. G., C. H. Song, H. K. Yi, P. H. Hwang, J. S. Kim, K. S. Lee, and Y. C. Lee. 2003. Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma. J. Clin. Invest. 111: 1083-1092.
30. Lacalle, R. A., C. Gómez-Moutón, D. F. Barber, S. Jiménez-Baranda, E. Mira, C. Martínez-A, A. C. Carrera, and S. Mañes. 2004. PTEN regulates motility but not directionality during leukocyte chemotaxis. J. Cell Sci. 117: 6207-6215. (Pubitemid 40123984)
31. Tamura, M., J. Gu, K. Matsumoto, S. Aota, R. Parsons, and K. M. Yamada. 1998. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280: 1614-1617. (Pubitemid 28277707)
32. Subramanian, K. K., Y. Jia, D. Zhu, B. T. Simms, H. Jo, H. Hattori, J. You, J. P. Mizgerd, and H. R. Luo. 2007. Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated neutrophil functions. Blood 109: 4028-4037. (Pubitemid 46641758)
33. Schabbauer, G., U. Matt, P. Günzl, J.Warszawska, T. Furtner, E. Hainzl, I. Elbau, I. Mesteri, B. Doninger, B. R. Binder, and S. Knapp. 2010. Myeloid PTEN promotes inflammation but impairs bactericidal activities during murine pneumococcal pneumonia. J. Immunol. 185: 468-476.
34. Li, Y., Y. Jia, M. Pichavant, F. Loison, B. Sarraj, A. Kasorn, J. You, B. E. Robson, D. T. Umetsu, J. P. Mizgerd, et al. 2009. Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia. Blood 113: 4930-4941.
35. Gu, Y., M. D. Filippi, J. A. Cancelas, J. E. Siefring, E. P. Williams, A. C. Jasti, C. E. Harris, A. W. Lee, R. Prabhakar, S. J. Atkinson, et al. 2003. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 302: 445-449. (Pubitemid 37296270)
36. Roberts, A. W., C. Kim, L. Zhen, J. B. Lowe, R. Kapur, B. Petryniak, A. Spaetti, J. D. Pollock, J. B. Borneo, G. B. Bradford, et al. 1999. Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 10: 183-196. (Pubitemid 29115624)
37. Corbetta, S., S. Gualdoni, C. Albertinazzi, S. Paris, L. Croci, G. G. Consalez, and I. de Curtis. 2005. Generation and characterization of Rac3 knockout mice. Mol. Cell. Biol. 25: 5763-5776. (Pubitemid 40853608)
38. Kamen, L. A., J. Levinsohn, and J. A. Swanson. 2007. Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes. Mol. Biol. Cell 18: 2463-2472. (Pubitemid 47025712)
39. Leverrier, Y., K. Okkenhaug, C. Sawyer, A. Bilancio, B. Vanhaesebroeck, and A. J. Ridley. 2003. Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophages. J. Biol. Chem. 278: 38437-38442. (Pubitemid 37221737)
40. Torres, J., and R. Pulido. 2001. The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J. Biol. Chem. 276: 993-998. (Pubitemid 32096519)
41. Vazquez, F., S. Ramaswamy, N. Nakamura, and W. R. Sellers. 2000. Phosphorylation of the PTEN tail regulates protein stability and function. Mol. Cell. Biol. 20: 5010-5018. (Pubitemid 30431555)
42. Martin, M., K. Rehani, R. S. Jope, and S. M. Michalek. 2005. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat. Immunol. 6: 777-784. (Pubitemid 43090463)
43. Martin, M., R. E. Schifferle, N. Cuesta, S. N. Vogel, J. Katz, and S. M. Michalek. 2003. Role of the phosphatidylinositol 3 kinase-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J. Immunol. 171: 717-725. (Pubitemid 36871381)
44. Luyendyk, J. P., G. A. Schabbauer, M. Tencati, T. Holscher, R. Pawlinski, and N. Mackman. 2008. Genetic analysis of the role of the PI3K-Akt pathway in lipopolysaccharide-induced cytokine and tissue factor gene expression in monocytes/macrophages. J. Immunol. 180: 4218-4226.
45. Wang, H., J. Brown, Z. Gu, C. A. Garcia, R. Liang, P. Alard, E. Beurel, R. S. Jope, T. Greenway, and M. Martin. 2011. Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-b-signaling pathways regulates the innate inflammatory response. J. Immunol. 186: 5217-5226.
46. Wang, H., J. Brown, C. A. Garcia, Y. Tang, M. R. Benakanakere, T. Greenway, P. Alard, D. F. Kinane, and M. Martin. 2011. The role of glycogen synthase kinase 3 in regulating IFN-b-mediated IL-10 production. J. Immunol. 186: 675-684.
47. Wang, H., J. Brown, and M. Martin. 2011. Glycogen synthase kinase 3: a point of convergence for the host inflammatory response. Cytokine 53: 130-140.
48. Pengal, R. A., L. P. Ganesan, G. Wei, H. Fang, M. C. Ostrowski, and S. Tridandapani. 2006. Lipopolysaccharide-induced production of interleukin-10 is promoted by the serine/threonine kinase Akt. Mol. Immunol. 43: 1557-1564.
49. Wells, C. M., M. Walmsley, S. Ooi, V. Tybulewicz, and A. J. Ridley. 2004. Rac1- deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration. J. Cell Sci. 117: 1259-1268. (Pubitemid 38456106)
50. Yamauchi, A., C. Kim, S. Li, C. C. Marchal, J. Towe, S. J. Atkinson, and M. C. Dinauer. 2004. Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles. J. Immunol. 173: 5971-5979. (Pubitemid 39487751)
51. Mahajan, N. P., and H. S. Earp. 2003. An SH2 domain-dependent, phosphotyrosine- independent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing guanine nucleotide-exchange factor action. J. Biol. Chem. 278: 42596-42603. (Pubitemid 37310533)
52. Grommes, C., C. Y. Lee, B. L. Wilkinson, Q. Jiang, J. L. Koenigsknecht-Talboo, B. Varnum, and G. E. Landreth. 2008. Regulation of microglial phagocytosis and inflammatory gene expression by Gas6 acting on the Axl/Mer family of tyrosine kinases. J. Neuroimmune Pharmacol. 3: 130-140.
53. Gao, C., E. Schaefer, M. Lakkis, and S. D. Blystone. 2005. Beta3 tyrosine phosphorylation and alphavbeta3-mediated adhesion are required for Vav1 association and Rho activation in leukocytes. J. Biol. Chem. 280: 15422-15429. (Pubitemid 40562900)
54. Cichowski, K., J. S. Brugge, and L. F. Brass. 1996. Thrombin receptor activation and integrin engagement stimulate tyrosine phosphorylation of the proto-oncogene product, p95vav, in platelets. J. Biol. Chem. 271: 7544-7550.
55. Papakonstanti, E. A., A. J. Ridley, and B. Vanhaesebroeck. 2007. The p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN. EMBO J. 26: 3050-3061. (Pubitemid 47057501)
56. Li, Z., X. Dong, Z. Wang, W. Liu, N. Deng, Y. Ding, L. Tang, T. Hla, R. Zeng, L. Li, and D. Wu. 2005. Regulation of PTEN by Rho small GTPases. Nat. Cell Biol. 7: 399-404. (Pubitemid 40533130)
57. Nakaya, M., M. Tanaka, Y. Okabe, R. Hanayama, and S. Nagata. 2006. Opposite effects of rho family GTPases on engulfment of apoptotic cells by macrophages. J. Biol. Chem. 281: 8836-8842. (Pubitemid 43847990)
58. Tosello-Trampont, A. C., K. Nakada-Tsukui, and K. S. Ravichandran. 2003. Engulfment of apoptotic cells is negatively regulated by Rho-mediated signaling. J. Biol. Chem. 278: 49911-49919. (Pubitemid 37548826)
59. Strassheim, D., J. Y. Kim, J. S. Park, S. Mitra, and E. Abraham. 2005. Involvement of SHIP in TLR2-induced neutrophil activation and acute lung injury. J. Immunol. 174: 8064-8071. (Pubitemid 40806317)
60. Williams, D. L., C. Li, T. Ha, T. Ozment-Skelton, J. H. Kalbfleisch, J. Preiszner, L. Brooks, K. Breuel, and J. B. Schweitzer. 2004. Modulation of the phosphoinositide 3-kinase pathway alters innate resistance to polymicrobial sepsis. J. Immunol. 172: 449-456. (Pubitemid 38020500)
61. Schabbauer, G., J. Luyendyk, K. Crozat, Z. Jiang, N. Mackman, S. Bahram, and P. Georgel. 2008. TLR4/CD14-mediated PI3K activation is an essential component of interferon-dependent VSV resistance in macrophages. Mol. Immunol. 45: 2790-2796.
62. Sen, P., M. A. Wallet, Z. Yi, Y. Huang, M. Henderson, C. E. Mathews, H. S. Earp, G. Matsushima, A. S. Baldwin, Jr., and R. M. Tisch. 2007. Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood 109: 653-660. (Pubitemid 46105966)
63. Kim, J. S., X. Peng, P. K. De, R. L. Geahlen, and D. L. Durden. 2002. PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac. Blood 99: 694-697 (Pubitemid 34533110)