Regulation of phagocytosis by TAM receptors and their ligands

Frontiers of Biology in China

Volumn 5, Issue 3, 2010, Pages 227-237

  Lu, Qingxian ^a,b   Li, Qiutang ^a   Lu, Qingjun ^b,c  

^a University of Louisville School of Medicine   (United States)

^b CAPITAL MEDICAL UNIVERSITY   (China)

^c BEIJING INSTITUTE OF OPHTHALMOLOGY   (China)

Author keywords

Growth arrest specific gene 6 (Gas 6); Ligands; Phagocytosis; Protein S; Regulation; TAM family (Tyro3, Axl and Mertk)

Indexed keywords

EID: 77953627371     PISSN: 16733509     EISSN: 16733622     Source Type: Journal    
DOI: 10.1007/s11515-010-0034-5     Document Type: Review

References (108)

1. Ait-Oufella H, Pouresmail V, Simon T, Blanc-Brude O, Kinugawa K, Merval R, Offenstadt G, Lesèche G, Cohen P L, Tedgui A, Mallat Z (2008). Defective mer receptor tyrosine kinase signaling in bone marrow cells promotes apoptotic cell accumulation and accelerates atherosclerosis. Arterioscler Thromb Vasc Biol, 28(8): 1429-1431.
2. Anderson H A, Maylock C A, Williams J A, Paweletz C P, Shu H, Shacter E (2003). Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol, 4(1): 87-91.
3. Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F, Arnout J, Dewerchin M, Hoylaerts M, Herbert J, Collen D, Dahlbäck B, Carmeliet P (2001). Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med, 7(2): 215-221.
4. Araki N, Johnson MT, Swanson J A (1996). A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol, 135(5): 1249-1260.
5. Bellosta P, Zhang Q, Goff S P, Basilico C (1997). Signaling through the ARK tyrosine kinase receptor protects from apoptosis in the absence of growth stimulation. Oncogene, 15(20): 2387-2397.
6. Bernstein P S, Law W C, Rando R R (1987). Biochemical characterization of the retinoid isomerase system of the eye. J Biol Chem, 262(35): 16848-16857.
7. Bok D, Hall M O (1971). The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the rat. J Cell Biol, 49(3): 664-682.
8. Braunger J, Schleithoff L, Schulz A S, Kessler H, Lammers R, Ullrich A, Bartram C R, Janssen J W (1997). Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene, 14(22): 2619-2631.
9. Burstyn-Cohen T, Heeb MJ, Lemke G (2009). Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis. J Clin Invest, 119(10): 2942-2953.
10. Camenisch T D, Koller B H, Earp H S, Matsushima G K (1999). A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and lipopolysaccharide-induced endotoxic shock. J Immunol, 162(6): 3498-3503.
11. Caraux A, Lu Q, Fernandez N, Riou S, Di Santo J P, Raulet D H, Lemke G, Roth C (2006). Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases. Nat Immunol, 7(7): 747-754.
12. Charbel Issa P, Bolz H J, Ebermann I, Domeier E, Holz F G, Scholl H P (2009). Characterisation of severe rod-cone dystrophy in a consanguineous family with a splice site mutation in the MERTK gene. Br J Ophthalmol, 93(7): 920-925.
13. Chen J, Carey K, Godowski P J (1997). Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation. Oncogene, 14(17): 2033-2039.
14. D'Angelo A, Viganò D'Angelo S (2008). Protein S deficiency. Haematologica, 93(4): 498-501.
15. D'Cruz P M, Yasumura D, Weir J, Matthes M T, Abderrahim H, LaVail M M, Vollrath D (2000). Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet, 9(4): 645-651.
16. Dahlbäck B (1991). Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system. Thromb Haemost, 66(1): 49-61.
17. Dowling J E, Sidman R L (1962). Inherited retinal dystrophy in the rat. J Cell Biol, 14: 73-109.
18. Duncan J L, LaVail M M, Yasumura D, Matthes M T, Yang H, Trautmann N, Chappelow A V, Feng W, Earp H S, Matsushima G K, Vollrath D (2003a). An RCS-like retinal dystrophy phenotype in mer knockout mice. Invest Ophthalmol Vis Sci, 44(2): 826-838.
19. Duncan J L, Yang H, Vollrath D, Yasumura D, Matthes M T, Trautmann N, Chappelow A V, Feng W, Earp H S, Matsushima G K, LaVail M M (2003b). Inherited retinal dystrophy in Mer knockout mice. Adv Exp Med Biol, 533: 165-172.
20. Edwards R B, Szamier R B (1977). Defective phagocytosis of isolated rod outer segments by RCS rat retinal pigment epithelium in culture. Science, 197(4307): 1001-1003.
21. Feng W, Yasumura D, Matthes M T, LaVail M M, Vollrath D (2002). Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells. J Biol Chem, 277(19): 17016-17022.
22. Finnemann S C (2003). Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J, 22(16): 4143-4154.
23. Finnemann S C, Rodriguez-Boulan E (1999). Macrophage and retinal pigment epithelium phagocytosis: apoptotic cells and photoreceptors compete for alphavbeta3 and alphavbeta5 integrins, and protein kinase C regulates alphavbeta5 binding and cytoskeletal linkage. J Exp Med, 190(6): 861-874.
24. Gal A, Li Y, Thompson D A, Weir J, Orth U, Jacobson S G, Apfelstedt-Sylla E, Vollrath D (2000). Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet, 26(3): 270-271.
25. García de Frutos P, Fuentes-Prior P, Hurtado B, Sala N (2007). Molecular basis of protein S deficiency. Thromb Haemost, 98(3): 543-556.
26. Georgescu M M, Kirsch K H, Shishido T, Zong C, Hanafusa H (1999). Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NF-kappaB. Mol Cell Biol, 19(2): 1171-1181.
27. Godowski P J, Mark MR, Chen J, Sadick MD, Raab H, Hammonds R G (1995). Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3. Cell, 82(3): 355-358.
28. Graham D K, Dawson T L, Mullaney D L, Snodgrass H R, Earp H S (1994). Cloning and mRNA expression analysis of a novel human protooncogene, c-mer. Cell Growth Differ, 5(6): 647-657.
29. Hafizi S, Dahlbäck B (2006). Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev, 17(4): 295-304.
30. Hall M O, Abrams T (1987). Kinetic studies of rod outer segment binding and ingestion by cultured rat RPE cells. Exp Eye Res, 45(6): 907-922.
31. Hall M O, Agnew B J, Abrams T A, Burgess B L (2003). The phagocytosis of os is mediated by the PI3-kinase linked tyrosine kinase receptor, mer, and is stimulated by GAS6. Adv Exp Med Biol, 533: 331-336.
32. Hall M O, Obin M S, Heeb M J, Burgess B L, Abrams T A (2005). Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat retinal pigment epithelial cells. Exp Eye Res, 81(5): 581-591.
33. Hall M O, Obin M S, Prieto A L, Burgess B L, Abrams T A (2002). Gas6 binding to photoreceptor outer segments requires gamma-carboxyglutamic acid (Gla) and Ca(2 +) and is required for OS phagocytosis by RPE cells in vitro. Exp Eye Res, 75(4): 391-400.
34. Hall M O, Prieto A L, Obin M S, Abrams T A, Burgess B L, Heeb M J, Agnew B J (2001). Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6. Exp Eye Res, 73(4): 509-520.
35. Hasanbasic I, Rajotte I, Blostein M (2005). The role of gamma-carboxylation in the anti-apoptotic function of gas6. J Thromb Haemost, 3(12): 2790-2797.
36. Huang M, Rigby A C, Morelli X, Grant M A, Huang G, Furie B, Seaton B, Furie B C (2003). Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins. Nat Struct Biol, 10(9): 751-756.
37. Hubbard S R, Mohammadi M, Schlessinger J (1998). Autoregulatory mechanisms in protein-tyrosine kinases. J Biol Chem, 273(20): 11987-11990.
38. Hubbard S R, Till J H (2000). Protein tyrosine kinase structure and function. Annu Rev Biochem, 69: 373-398.
39. Ishimoto Y, Ohashi K, Mizuno K, Nakano T (2000). Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J Biochem, 127(3): 411-417.
40. Janssen J W, Schulz A S, Steenvoorden A C, Schmidberger M, Strehl S, Ambros P F, Bartram C R (1991). A novel putative tyrosine kinase receptor with oncogenic potential. Oncogene, 6(11): 2113-2120.
41. Jia R, Hanafusa H (1994). The proto-oncogene of v-eyk (v-ryk) is a novel receptor-type protein tyrosine kinase with extracellular Ig/GNIII domains. J Biol Chem, 269(3): 1839-1844.
42. Kamen L A, Levinsohn J, Swanson J A (2007). Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes. Mol Biol Cell. 8(7): 2463-2472.
43. Keating A K, Salzberg D B, Sather S, Liang X, Nickoloff S, Anwar A, Deryckere D, Hill K, Joung D, Sawczyn K K, Park J, Curran-Everett D, McGavran L, Meltesen L, Gore L, Johnson G L, Graham D K (2006). Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase. Oncogene, 25(45): 6092-6100.
44. Lai C, Gore M, Lemke G (1994). Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase. Oncogene, 9(9): 2567-2578.
45. LaVail M M (1973). Kinetics of rod outer segment renewal in the developing mouse retina. J Cell Biol, 58(3): 650-661.
46. LaVail M M (1976). Rod outer segment disk shedding in rat retina: relationship to cyclic lighting. Science, 194(4269): 1071-1074.
47. Lemke G, Lu Q (2003). Macrophage regulation by Tyro 3 family receptors. Curr Opin Immunol, 15(1): 31-36.
48. Lemke G, Rothlin C V (2008). Immunobiology of the TAM receptors. Nat Rev Immunol, 8(5): 327-336.
49. Lu Q, Gore M, Zhang Q, Camenisch T, Boast S, Casagranda F, Lai C, Skinner M K, Klein R, Matsushima G K, Earp H S, Goff S P, Lemke G (1999). Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature, 398(6729): 723-728.
50. Lu Q, Lemke G (2001). Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science, 293(5528): 306-311.
51. Lundwall A, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlbäck B, Stenflo J, Wydro R (1986). Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc Natl Acad Sci U S A, 83(18): 6716-6720.
52. Maeda Y, Shiratsuchi A, Namiki M, Nakanishi Y (2002). Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility. Cell Death Differ, 9(7): 742-749.
53. Maguire A M, Simonelli F, Pierce E A, Pugh E N Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall K A, Testa F, Surace E M, Rossi S, Lyubarsky A, Arruda V R, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma J X, Redmond T M, Zhu X, Hauck B, Zelenaia O, Shindler K S, Maguire M G, Wright J F, Volpe N J, McDonnell J W, Auricchio A, High K A, Bennett J (2008). Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med, 358(21): 2240-2248.
54. Mahajan N P, Earp H S (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(43): 42596-42603.
55. Manfioletti G, Brancolini C, Avanzi G, Schneider C (1993). The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol, 13(8): 4976-4985.
56. Manning G, Whyte D B, Martinez R, Hunter T, Sudarsanam S (2002). The protein kinase complement of the human genome. Science, 298(5600): 1912-1934.
57. Mark M R, Chen J, Hammonds R G, Sadick M, Godowsk P J (1996). Characterization of Gas6, a member of the superfamily of G domaincontaining proteins, as a ligand for Rse and Axl. J Biol Chem, 271(16): 9785-9789.
58. May R C, Machesky L M (2001). Phagocytosis and the actin cytoskeleton. J Cell Sci, 114(Pt 6): 1061-1077.
59. Mayerson P L, Hall M O (1986). Rat retinal pigment epithelial cells show specificity of phagocytosis in vitro. J Cell Biol, 103(1): 299-308.
60. Mays R W, Beck K A, Nelson W J (1994). Organization and function of the cytoskeleton in polarized epithelial cells: a component of the protein sorting machinery. Curr Opin Cell Biol, 6(1): 16-24.
61. McHenry C L, Liu Y, Feng W, Nair A R, Feathers K L, Ding X, Gal A, Vollrath D, Sieving P A, Thompson D A (2004). MERTK arginine-844-cysteine in a patient with severe rod-cone dystrophy: loss of mutant protein function in transfected cells. Invest Ophthalmol Vis Sci, 45(5): 1456-1463.
62. Miething A (1992). Germ-cell death during prespermatogenesis in the testis of the golden hamster. Cell Tissue Res, 267(3): 583-590.
63. Miljanich G P, Nemes P P, White D L, Dratz E A (1981). The asymmetric transmembrane distribution of phosphatidylethanolamine, phosphatidylserine, and fatty acids of the bovine retinal rod outer segment disk membrane. J Membr Biol, 60(3): 249-255.
64. Mullen R J, LaVail M M (1976). Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras. Science, 192(4241): 799-801.
65. Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (1996). Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem, 271(47): 30022-30027.
66. Nakano T, Ishimoto Y, Kishino J, Umeda M, Inoue K, Nagata K, Ohashi K, Mizuno K, Arita H (1997). Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6. J Biol Chem, 272(47): 29411-29414.
67. Nakano T, Kawamoto K, Kishino J, Nomura K, Higashino K, Arita H (1997). Requirement of gamma-carboxyglutamic acid residues for the biological activity of Gas6: contribution of endogenous Gas6 to the proliferation of vascular smooth muscle cells. Biochem J, 323(Pt 2): 387-392.
68. Nandrot E, Dufour E M, Provost A C, Péquignot M O, Bonnel S, Gogat K, Marchant D, Rouillac C, Sépulchre de Condé B, Bihoreau M T, Shaver C, Dufier J L, Marsac C, Lathrop M, Menasche M, Abitbol M M (2000). Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis. Neurobiol Dis, 7(6 Pt B): 586-599.
69. Nandrot E F, Anand M, Sircar M, Finnemann S C (2006). Novel role for alphavbeta5-integrin in retinal adhesion and its diurnal peak. Am J Physiol Cell Physiol, 290(4): C1256-C1262.
70. Nandrot E F, Kim Y, Brodie S E, Huang X, Sheppard D, Finnemann S C (2004). Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin. J Exp Med, 200(12): 1539-1545.
71. Niedergang F, Chavrier P (2004). Signaling and membrane dynamics during phagocytosis: many roads lead to the phagos(R)ome. Curr Opin Cell Biol, 16(4): 422-428.
72. O'Bryan J P, Frye R A, Cogswell P C, Neubauer A, Kitch B, Prokop C, Espinosa R 3rd, Le Beau M M, Earp H S, Liu E T (1991). axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol Cell Biol, 11(10): 5016-5031.
73. Ohashi K, Mizuno K, Kuma K, Miyata T, Nakamura T (1994). Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain. Oncogene, 9(3): 699-705.
74. Prasad D, Rothlin C V, Burrola P, Burstyn-Cohen T, Lu Q, Garcia de Frutos P, Lemke G (2006). TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci, 33(1): 96-108.
75. Rescigno J, Mansukhani A, Basilico C (1991). A putative receptor tyrosine kinase with unique structural topology. Oncogene, 6(10): 1909-1913.
76. Robinson D R, Wu Y M, Lin S F (2000). The protein tyrosine kinase family of the human genome. Oncogene, 19(49): 5548-5557.
77. Rothlin C V, Ghosh S, Zuniga E I, Oldstone M B, Lemke G (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell, 131(6): 1124-1136.
78. Saller F, Brisset A C, Tchaikovski S N, Azevedo M, Chrast R, Fernández J A, Schapira M, Hackeng T M, Griffin J H, Angelillo-Scherrer A (2009). Generation and phenotypic analysis of protein S-deficient mice. Blood, 114(11): 2307-2314.
79. Sasaki T, Knyazev P G, Cheburkin Y, Göhring W, Tisi D, Ullrich A, Timpl R, Hohenester E (2002). Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains. J Biol Chem, 277(46): 44164-44170.
80. Sasaki T, Knyazev P G, Clout N J, Cheburkin Y, Göhring W, Ullrich A, Timpl R, Hohenester E (2006). Structural basis for Gas6-Axl signalling. EMBO J, 25(1): 80-87.
81. Sather S, Kenyon K D, Lefkowitz J B, Liang X, Varnum B C, Henson P M, Graham D K (2007). A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood, 109(3): 1026-1033.
82. Schlessinger J (2000). Cell signaling by receptor tyrosine kinases. Cell, 103(2): 211-225.
83. Schneider C, King R M, Philipson L (1988). Genes specifically expressed at growth arrest of mammalian cells. Cell, 54(6): 787-793.
84. Scott R S, McMahon E J, Pop S M, Reap E A, Caricchio R, Cohen P L, Earp H S, Matsushima G K (2001). Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature, 411(6834): 207-211.
85. Seitz H M, Camenisch T D, Lemke G, Earp H S, Matsushima G K (2007). Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol, 178(9): 5635-5642.
86. Sen P, Wallet MA, Yi Z, Huang Y, Henderson M, Mathews C E, Earp H S, Matsushima G, Baldwin A S Jr, Tisch R M (2007). Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood, 109(2): 653-660.
87. Shankar S L, O'Guin K, Cammer M, McMorris F A, Stitt T N, Basch R S, Varnum B, Shafit-Zagardo B (2003). The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway. J Neurosci, 23(10): 4208-4218.
88. Shankar S L, O'Guin K, Kim M, Varnum B, Lemke G, Brosnan C F, Shafit-Zagardo B (2006). Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis. J Neurosci, 26(21): 5638-5648.
89. Smith A J, Schlichtenbrede F C, Tschernutter M, Bainbridge J W, Thrasher A J, Ali R R (2003). AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa. Mol Ther, 8(2): 188-195.
90. Songyang Z, Shoelson S E, Chaudhuri M, Gish G, Pawson T, Haser W G, King F, Roberts T, Ratnofsky S, Lechleider R J, et al (1993). SH2 domains recognize specific phosphopeptide sequences. Cell, 72(5): 767-778.
91. Stitt T N, Conn G, Gore M, Lai C, Bruno J, Radziejewski C, Mattsson K, Fisher J, Gies D R, Jones P F, et al (1995). The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell, 80(4): 661-670.
92. Sugo T, Dahlbäck B, Holmgren A, Stenflo J (1986). Calcium binding of bovine protein S. Effect of thrombin cleavage and removal of the gamma-carboxyglutamic acid-containing region. J Biol Chem, 261(11): 5116-5120.
93. Swanson J A, Johnson M T, Beningo K, Post P, Mooseker M, Araki N (1999). A contractile activity that closes phagosomes in macrophages. J Cell Sci, 112(Pt 3): 307-316.
94. Taylor P R, Carugati A, Fadok V A, Cook H T, Andrews M, Carroll M C, Savill J S, Henson P M, Botto M, Walport M J (2000). A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med, 192(3): 359-366.
95. Thorp E, Cui D, Schrijvers D M, Kuriakose G, Tabas I (2008). Mertk receptor mutation reduces efferocytosis efficiency and promotes apoptotic cell accumulation and plaque necrosis in atherosclerotic lesions of apoe-/- mice. Arterioscler Thromb Vasc Biol, 28(8): 1421-1428.
96. Thorp E, Li Y, Bao L, Yao P M, Kuriakose G, Rong J, Fisher E A, Tabas I (2009). Brief report: increased apoptosis in advanced atherosclerotic lesions of Apoe-/- mice lacking macrophage Bcl-2. Arterioscler Thromb Vasc Biol, 29(2): 169-172.
97. Tibrewal N, Wu Y, D'mello V, Akakura R, George T C, Varnum B, Birge R B (2008). Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation. J Biol Chem, 283(6): 3618-3627.
98. Todt J C, Hu B, Curtis J L (2004). The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages. J Leukoc Biol, 75(4): 705-713.
99. Tschernutter M, Jenkins S A, Waseem N H, Saihan Z, Holder G E, Bird A C, Bhattacharya S S, Ali R R, Webster A R (2006). Clinical characterisation of a family with retinal dystrophy caused by mutation in the Mertk gene. Br J Ophthalmol, 90(6): 718-723.
100. Tschernutter M, Schlichtenbrede F C, Howe S, Balaggan K S, Munro P M, Bainbridge J W, Thrasher A J, Smith A J, Ali R R (2005). Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther, 12(8): 694-701.
101. Vollrath D, Feng W, Duncan J L, Yasumura D, D'Cruz P M, Chappelow A, Matthes M T, Kay M A, LaVail M M (2001). Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci U S A, 98(22): 12584-12589.
102. Wang H, Wang H, Xiong W, Chen Y, Ma Q, Ma J, Ge Y, Han D (2006). Evaluation on the phagocytosis of apoptotic spermatogenic cells by Sertoli cells in vitro through detecting lipid droplet formation by Oil Red O staining. Reproduction, 132(3): 485-492.
103. Williams J C, Craven R R, Earp H S, Kawula T H, Matsushima G K (2009). TAM receptors are dispensable in the phagocytosis and killing of bacteria. Cell Immunol, 259(2): 128-134.
104. Wu Y, Singh S, Georgescu M M, Birge R B (2005). A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci, 118(Pt 3): 539-553.
105. Xiong W, Chen Y, Wang H, Wang H, Wu H, Lu Q, Han D (2008). Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction, 135(1): 77-87.
106. Young R W (1967). The renewal of photoreceptor cell outer segments. J Cell Biol, 33(1): 61-72.
107. Young R W, Bok D (1969). Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol, 42(2): 392-403.
108. Zheng Y, Zhang L, Lu Q, Wang X, Yu F, Wang X, Lu Q (2009). NGF-induced Tyro3 and Axl function as survival factors for differentiating PC12 cells. Biochem Biophys Res Commun, 378(3): 371-375.