Skip to main content
SpringerLink
Log in

Plasma Growth Arrest-Specific Protein 6 (Gas6) as a Biomarker of Renal Diseases

  • Reference work entry
  • First Online:
Biomarkers in Kidney Disease

  • 1425 Accesses

Abstract

Gas6 (growth arrest-specific 6) is a unique protein belonging to the family of plasma vitamin K-dependent proteins and a ligand for the tyrosine kinase family (Tyro3, Axl, Mer). Gas6 bears a great structural resemblance to the anticoagulant protein S. Interestingly, in spite of the presence of a g-carboxyglutamic acid domain in its structure, Gas6 has not been discored to show any function in the coagulation cascade. Gas6 has been reported to participate in cell proliferation, apoptosis, chemotaxis, leukocyte migration, sequestration, platelet aggregation, vascular homeostasis, and inflammation. In addition, it plays a role in the activation of various kinds of cells, including platelets and endothelial and vascular smooth-muscle cells (VSMC). After it was demonstrated that Gas6 induces proliferation of VSMC and serum-starved NIH 3T3 (mouse embryonic fibroblast cell lines) fibroblasts, mitogenic effects of Gas6 were found in cultured mesangial cells. As a result, it has been reported to take part in various pathophysiological processes, for instance, atherosclerosis, renal diseases, cancer, and thrombosis. The main subject of the present review is the role Gas6 plays in renal diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 449.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

Ang:

Angiotensin

CKD:

Chronic kidney disease

CR:

Chronic rejection

DN:

Diabetic nephropathy

DOCA:

Deoxycorticosterone acetate

EC:

Endothelial cells

ECM:

Extracellular matrix

ELISA:

Enzyme-linked immunosorbent assay

Gas6:

Growth arrest-specific gene protein 6

GFR:

Glomerular filtration rate

Gla:

g-Carboxyglutamic acid

GN:

Glomerulonephritis

GO:

Glycoxidized

HD:

Hemodialysis

IgAN:

IgA nephropathy

IMT:

Intima-media thickening

LDL:

Low-density lipoprotein

MHC:

Myosin heavy chain

MMCs:

Mouse mesangial cells

MR:

Mineralocorticoid receptor

NADPH:

Nicotinamide adenine dinucleotide phosphate

NIH 3T3:

Mouse embryonic fibroblast cell lines

NK:

Natural killer

NTN:

Nephrotoxic nephritis

NTS:

Nephrotoxic serum

PDGF:

Platelet-derived growth factor

PI3K:

Phosphatidylinositol-3-kinase

RAAS:

Renin-angiotensin-aldosterone system

RCC:

Renal cell carcinoma

RTK:

Receptor tyrosine kinase

RT-PCR:

Reverse transcription polymerase chain reaction

SHGB:

Sex hormone-binding globulin

STAT:

Signal transducers and activators of transcription

STZ:

Streptozotocin

TAM receptors:

Tyro3, Axl, and Mer receptors

TGF-β:

Transforming growth factor beta

TNF:

Tumor necrosis factor

VKD:

Vitamin K-dependent

VSMC:

Vascular smooth-muscle cells

References

  • Allen MP, Zeng C, Schneider K, et al. Growth arrest-specific gene 6 (Gas6)/adhesion related kinase (Ark) signaling promotes gonadotropin-releasing hormone neuronal survival via extracellular signal-regulated kinase (ERK) and Akt. Mol Endocrinol. 1999;13:191–201.

    Article  CAS  PubMed  Google Scholar 

  • Angelillo-Scherrer A, García de Frutos P, Aparicio C, et al. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med. 2001;7:215–21.

    Article  CAS  PubMed  Google Scholar 

  • Angelillo-Scherrer A, Burnier L, Flores N, et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest. 2005;115:237–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007;13:9–20.

    PubMed  Google Scholar 

  • Avanzi GC, Gallicchio M, Cavalloni G, et al. GAS6, the ligand of Axl and Rse receptors, is expressed in hematopoietic tissue but lacks mitogenic activity. Exp Hematol. 1997;25:1219–26.

    CAS  PubMed  Google Scholar 

  • Avanzi GC, Gallicchio M, Bottarel F, et al. GAS6 inhibits granulocyte adhesion to endothelial cells. Blood. 1998;91:2334–40.

    CAS  PubMed  Google Scholar 

  • Balogh I, Hafizi S, Stenhoff J, et al. Analysis of Gas6 in human platelets and plasma. Arterioscler Thromb Vasc Biol. 2005;25:1280–6.

    Article  CAS  PubMed  Google Scholar 

  • Batchu SN, Hughso A, Gerloff J, et al. Role of Axl in early kidney inflammation and progression of salt-dependent hypertension. Hypertension. 2013;62:302–9.

    Article  CAS  PubMed  Google Scholar 

  • Bellido-Martín L, Frutos PG. Vitamin K-dependent actions of Gas6. Vitam Horm. 2008;78:185–209.

    Article  PubMed  Google Scholar 

  • Bellosta P, Costa M, Lin DA, et al. The receptor tyrosine kinase ARK mediates cell aggregation by homophilic binding. Mol Cell Biol. 1995;15:614–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borgel D, Clauser S, Bornstain C, et al. Elevated growth-arrest-specific protein 6 plasma levels in patients with severe sepsis. Crit Care Med. 2006;34:219–22.

    Article  CAS  PubMed  Google Scholar 

  • Caraux A, Lu Q, Fernandez N, et al. Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases. Nat Immunol. 2006;7:747–54.

    Article  CAS  PubMed  Google Scholar 

  • Cavet ME, Smolock EM, Ozturk OH, et al. Gas6-axl receptor signaling is regulated by glucose in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2008;28:886–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cavet ME, Smolock EM, Menon P, et al. Gas6-Axl pathway: the role of redox-dependent association of Axl with nonmuscle myosin IIB. Hypertension. 2010;56:105–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clauser S, Bachelot-Lozat C, Fontana P, et al. Physiological plasma Gas6 levels do not influence platelet aggregation. Arterioscler Thromb Vasc Biol. 2006;26:e22.

    Article  PubMed  Google Scholar 

  • Collett G, Wood A, Alexander MY, et al. Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes. Circ Res. 2003;92:1123–9.

    Article  CAS  PubMed  Google Scholar 

  • Collett GD, Sage AP, Kirton JP, et al. Axl/phosphatidylinositol 3-kinase signaling inhibits mineral deposition by vascular smooth muscle cells. Circ Res. 2007;100:502–9.

    Article  CAS  PubMed  Google Scholar 

  • Correll PH, Morrison AC, Lutz MA, et al. Receptor tyrosine kinases and the regulation of macrophage activation. J Leukoc Biol. 2004;75:731–7.

    Article  CAS  PubMed  Google Scholar 

  • Couchie D, Lafdil F, Martin-Garcia N, et al. Expression and role of Gas6 protein and of its receptor Axl in hepatic regeneration from oval cells in the rat. Gastroenterology. 2005;129:1633–42.

    Article  CAS  PubMed  Google Scholar 

  • Dahlbäck B, Villoutreix BO. Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol. 2005;25:1311–20.

    Article  PubMed  Google Scholar 

  • Demarchi F, Verardo R, Varnum B, et al. Gas6 anti-apoptotic signaling requires NF-kappa B activation. J Biol Chem. 2001;276:31738–44.

    Article  CAS  PubMed  Google Scholar 

  • Doi T. The contribution of mesangial cell proliferation to progressive glomerular injury. J Med Investig. 2001;48:1–4.

    CAS  Google Scholar 

  • Donate-Correa J, Martín-Núñez E, Muros-de-Fuentes M, et al. Inflammatory cytokines in diabetic nephropathy. J Diabetes Res. 2015;2015:948417.

    Article  PubMed  PubMed Central  Google Scholar 

  • Erek-Toprak A, Bingol-Ozakpinar O, Karaca Z, et al. Association of plasma growth arrest-specific protein 6 (Gas6) concentrations with albuminuria in patients with type 2 diabetes. Ren Fail. 2014;36:737–42.

    Article  CAS  PubMed  Google Scholar 

  • Erkoc R, Cikrikcioglu MA, Aintab E, et al. GAS6 intron 8 c.834+7G>A gene polymorphism in diabetic nephropathy, renal failure. Accepted 18 Mar 2015 ID:LRNF 2014 0756R1.

    Google Scholar 

  • Folli F, Okada T, Perego C, et al. Altered insulin receptor signalling and β-cell cycle dynamics in type 2 diabetes mellitus. PLoS One. 2011;6(11):e28050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fridell YW, Villa Jr J, Attar EC, et al. GAS6 induces Axl-mediated chemotaxis of vascular smooth cells. J Biol Chem. 1998;273:7123–6.

    Article  CAS  PubMed  Google Scholar 

  • Gallicchio M, Mitola S, Valdembri D, et al. Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial cell activation by Axl tyrosine kinase receptor. Blood. 2005;105:1970–6.

    Article  CAS  PubMed  Google Scholar 

  • Goruppi S, Ruaro E, Schneider C. Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts. Oncogene. 1996;12:471–80.

    CAS  PubMed  Google Scholar 

  • Goruppi S, Ruaro E, Varnum B. Gas6-mediated survival in NIH3T3 cells activates stress signalling cascade and is independent of Ras. Oncogene. 1999;18:4224–36.

    Article  CAS  PubMed  Google Scholar 

  • Gould WR, Baxi SM, Schroeder R, et al. Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses. J Thromb Haemost. 2005;3:733–41.

    Article  CAS  PubMed  Google Scholar 

  • Gustafsson A, Boström AK, Ljungberg B, et al. Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma. PLoS One. 2009a;4:e7575.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gustafsson A, Martuszewska D, Johansson M, et al. Differential expression of Axl and Gas6 in renal cell carcinoma reflecting tumor advancement and survival. Clin Cancer Res. 2009b;15:4742–9.

    Article  CAS  PubMed  Google Scholar 

  • Guttridge KL, Luft JC, Dawson TL, et al. Mer receptor tyrosine kinase signaling: prevention of apoptosis and alteration of cytoskeletal architecture without stimulation or proliferation. J Biol Chem. 2002;277:24057–66.

    Article  CAS  PubMed  Google Scholar 

  • Hafizi S, Alindri F, Karlsson R, et al. Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin. Biochem Biophys Res Commun. 2002;299:793–800.

    Article  CAS  PubMed  Google Scholar 

  • Hall MO, Prieto AL, Obin MS, et al. Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6. Exp Eye Res. 2001;73:509–20.

    Article  CAS  PubMed  Google Scholar 

  • Hansson K, Stenflo J. Post-translational modifications in proteins involved in blood coagulation. J Thromb Haemost. 2005;3:2633–48.

    Article  CAS  PubMed  Google Scholar 

  • Hasanbasic I, Cuerquis J, Varnum B, et al. Intracellular signaling pathways involved in Gas6-Axl-mediated survival of endothelial cells. Am J Physiol Heart Circ Physiol. 2004;287:1207–13.

    Article  Google Scholar 

  • He X, Shen L, Villoutreix BO, et al. Amino acid residues in thrombin-sensitive region and first epidermal growth factor domain of vitamin K-dependent protein S determining specificity of the activated protein C cofactor function. J Biol Chem. 1998;273:27449–58.

    Article  CAS  PubMed  Google Scholar 

  • Huang M, Rigby AC, Morelli X, et al. Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins. Nat Struct Biol. 2003;10:751–6.

    Article  CAS  PubMed  Google Scholar 

  • International Diabetes Federation Diabetes Atlas, 6th ed. http://www.idf.org/diabetesatlas/6e/Update20124. Accessed March 2015.

  • Ishimoto Y, Nakano T. Release of a product of growth arrest-specific gene 6 from rat platelets. FEBS Lett. 2000;466:197–9.

    Article  CAS  PubMed  Google Scholar 

  • Ishimoto Y, Ohashi K, Mizuno K, et al. Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J Biochem. 2000;127:411–7.

    Article  CAS  PubMed  Google Scholar 

  • Jonasch E, Gao J, Rathmell WK. Renal cell carcinoma. BMJ. 2014;349:g4797.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kawaguchi H, Katagir M, Chikazu D. Osteoclastic bone resorption through receptor tyrosine kinase and extracellular signal-regulated kinase signaling in mature osteoclasts. Mod Rheumatol. 2004;14:1–5.

    Article  PubMed  Google Scholar 

  • Kim HA, Nam JY, Jung JY, et al. Serum growth arrest-specific protein 6 levels are elevated in adult-onset Still’s disease. Clin Rheumatol. 2014;33:865–8.

    Article  PubMed  Google Scholar 

  • Konishi A, Aizawa T, Mohan A, et al. Hydrogen peroxide activates the Gas6-Axl pathway in vascular smooth muscle cells. J Biol Chem. 2004;279:28766–70.

    Article  CAS  PubMed  Google Scholar 

  • Korshunov VA, Mohan AM, Georger MA, et al. Axl, a receptor tyrosine kinase, mediates flow-induced vascular remodeling. Circ Res. 2006;98:1446–52.

    Article  CAS  PubMed  Google Scholar 

  • Laurance S, Lemarié CA, Blostein MD, et al. Growth Arrest-Specific Gene 6 (gas6) and Vascular Hemostasis. Adv Nutr. 2012;3:196–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee IJ, Hilliard B, Swami A, et al. Growth arrest-specific gene 6 (Gas6) levels are elevated in patients with chronic renal failure. Nephrol Dial Transplant. 2012;27:4166–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lemke G, Rothlin CV. Immunobiology of the TAM receptors. Nat Rev Immunol. 2008;8:327–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li R, Chen J, Hammonds G, et al. Identification of Gas6 as a growth factor for human Schwann cells. J Neurosci. 1996;16:2012–9.

    CAS  PubMed  Google Scholar 

  • Lutgens E, García de Frutos P, Aparicio C. Gas6−/−/ApoE−/− mice develop a collagen-rich, disorganized plaque phenotype, prone to intra-plaque hemorrhage. Circulation. 2000;102:38.

    Google Scholar 

  • Lyons TJ. Glycation and oxidation: a role in the pathogenesis of atherosclerosis. Am J Cardiol. 1993;71:26B–31.

    Article  CAS  PubMed  Google Scholar 

  • Manfioletti G, Brancolini C, Avanzi G, et al. 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. 1993;13:4976–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maquoi E, Voros G, Carmeliet P, et al. Role of Gas-6 in adipogenesis and nutritionally induced adipose tissue development in mice. Arterioscler Thromb Vasc Biol. 2005;25:1002–7.

    Article  CAS  PubMed  Google Scholar 

  • Melaragno MG, Wuthrich DA, Poppa V, et al. Increased expression of Axl tyrosine kinase after vascular injury and regulation by G protein-coupled receptor agonists in rats. Circ Res. 1998;83:697–704.

    Article  CAS  PubMed  Google Scholar 

  • Mima A, Arai H, Matsubara T, et al. Urinary Smad1 is a novel marker to predict later onset of mesangial matrix expansion in diabetic nephropathy. Diabetes. 2008;57:1712–22.

    Article  CAS  PubMed  Google Scholar 

  • Muñoz X, Obach V, Hurtado B, et al. Association of specific haplotypes of GAS6 gene with stroke. Thromb Haemost. 2007;98:406–12.

    PubMed  Google Scholar 

  • Murao K, Imachi H, Sayo Y, et al. A product of growth arrest-specific gene 6 modulates scavenger receptor expression in human vascular smooth muscle cells. FEBS Lett. 1999;459:363–6.

    Article  CAS  PubMed  Google Scholar 

  • Nagai K, Arai H, Yanagita M, et al. Growth arrest-specific gene 6 is involved in glomerular hypertrophy in the early stage of diabetic nephropathy. J Biol Chem. 2003;278:18229–34.

    Article  CAS  PubMed  Google Scholar 

  • Nagai K, Matsubara T, Mima A, et al. Gas6 induces Akt/mTOR-mediated mesangial hypertrophy in diabetic nephropathy. Kidney Int. 2005;68:552–61.

    Article  CAS  PubMed  Google Scholar 

  • Nagai K, Miyoshi M, Kake T, et al. Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy. PLoS One. 2013;8:e66759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagata K, Ohashi K, Nakano T, et al. 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. 1996;271:30022–7.

    Article  CAS  PubMed  Google Scholar 

  • Nakano T, Higashino K, Kikuchi N, et al. Vascular smooth muscle cell-derived, Gla-containing growth-potentiating factor for Ca(2+)-mobilizing growth factors. J Biol Chem. 1995;270:5702–5.

    Article  CAS  PubMed  Google Scholar 

  • Paul LC. Chronic renal transplant loss. Kidney Int. 1995;47:1491–9.

    Article  CAS  PubMed  Google Scholar 

  • Sather S, Kenyon KD, Lefkowitz JB, et al. A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood. 2007;109:1026–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlessinger J, Ullrich A. Growth factor signaling by receptor tyrosine kinases. Neuron. 1992;9:383–91.

    Article  CAS  PubMed  Google Scholar 

  • Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54:787–93.

    Article  CAS  PubMed  Google Scholar 

  • Sen P, Wallet MA, Yi Z, et al. Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood. 2007;109:653–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao WH, Zhen Y, Rosenbaum J, et al. A protective role of Mer receptor tyrosine kinase in nephrotoxic serum-induced nephritis. Clin Immunol. 2010;136:236–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shieh YS, Lai CY, Kao YR, et al. Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia. 2005;7:1058–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Son BK, Kozaki K, Iijima K, et al. Statins protect human aortic smooth muscle cells from inorganic phosphate-induced calcification by restoring Gas6-Axl survival pathway. Circ Res. 2006;98:1024–31.

    Article  CAS  PubMed  Google Scholar 

  • Son BK, Kozaki K, Iijima K, et al. Gas6/Axl-PI3K/Akt pathway plays a central role in the effect of statins on inorganic phosphate-induced calcification of vascular smooth muscle cells. Eur J Pharmacol. 2007;556:1–8.

    Article  CAS  PubMed  Google Scholar 

  • Stenhoff J, Dahlbäck B, Hafizi S. Vitamin K-dependent Gas6 activates ERK kinase and stimulates growth of cardiac fibroblasts. Biochem Biophys Res Commun. 2004;319:871–8.

    Article  CAS  PubMed  Google Scholar 

  • Su AI, Cooke MP, Ching KA, et al. Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci. 2002;99:4465–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tjwa M, Bellido-Martin L, Lin Y, et al. Gas6 promotes inflammation by enhancing interactions between endothelial cells, platelets, and leukocytes. Blood. 2008;111:4096–105.

    Article  CAS  PubMed  Google Scholar 

  • Topham PS, Csizmadia V, Soler D, et al. Lack of chemokine receptor CCR1 enhances Th1 responses and glomerular injury during nephrotoxic nephritis. J Clin Invest. 1999;104:1549–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tumlin JA, Madaio MP, Hennigar R. Idiopathic IgA nephropathy: pathogenesis, histopathology, and therapeutic options. Clin J Am Soc Nephrol. 2007;2:1054–61.

    Article  PubMed  Google Scholar 

  • Vajkoczy P, Knyazev P, Kunkel A, et al. Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival. Proc Natl Acad Sci. 2006;103:5799–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valverde P. Effects of Gas6 and hydrogen peroxide in Axl ubiquitination and downregulation. Biochem Biophys Res Commun. 2005;333:180–5.

    Article  CAS  PubMed  Google Scholar 

  • Van Ginkel PR, Gee RL, Shearer RL, et al. Expression of the receptor tyrosine kinase Axl promotes ocular melanoma cell survival. Cancer Res. 2004;64:128–34.

    Article  PubMed  Google Scholar 

  • Vandivier RW, Henson PM, Douglas IS. Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. Chest. 2006;129:1673–82.

    Article  PubMed  Google Scholar 

  • Villoutreix BO, de Frutos G, Lovenklev P, et al. SHBG region of the anticoagulant cofactor protein S: secondary structure prediction, circular dichroism spectroscopy, and analysis of naturally occurring mutations. Proteins. 1997;29:478–91.

    Article  CAS  PubMed  Google Scholar 

  • Waizenegger JS, Ben-Batalla I, Weinhold N, et al. Role of growth arrest-specific gene 6-Mer axis in multiple myeloma. Leukemia. 2015;29:696–704.

    Article  CAS  PubMed  Google Scholar 

  • Walzer T, Vivier E. NK cell development: gas matters. Nat Immunol. 2006;7:702–4.

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Chen S, Chen Y, et al. The role of Tyro 3 subfamily receptors in the regulation of hemostasis and megakaryocytopoiesis. Haematologica. 2007;92:643–50.

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Singh S, Georgescu MM, et al. A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci. 2005;118:539–53.

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Liu X, Koul S, et al. AXL kinase as a novel target for cancer therapy. Oncotarget. 2014;5:9546–63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yanagita M. Gas6, warfarin, and kidney diseases. Clin Exp Nephrol. 2004;8:304–9.

    Article  CAS  PubMed  Google Scholar 

  • Yanagita M, Arai H, Ishii K, et al. Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis. Am J Pathol. 2001a;158:1423–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yanagita M, Arai H, Nakano T, et al. Gas6 induces mesangial cell proliferation via latent transcription factor STAT3. J Biol Chem. 2001b;276:42364–9.

    Article  CAS  PubMed  Google Scholar 

  • Yanagita M, Ishimoto Y, Arai H, et al. Essential role of Gas6 for glomerular injury in nephrotoxic nephritis. J Clin Invest. 2002;110:239–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang ZX, Huang X, Jiang J,et al. Natural killer cells mediate long-term kidney allograft ınjury. transplantation. 2015 Feb 25. [Epub ahead of print].

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Göztepe Training and Research Hospital, Medical Biochemistry Lab, Istanbul Medeniyet University School of Medicine, Dr. Erkin Cad., 34730, Kadıkoy/Istanbul, Turkey

    Aybala Erek Toprak

Authors
  1. Aybala Erek Toprak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aybala Erek Toprak .

Editor information

Editors and Affiliations

  1. DeptofBiomedlSci,FacltyofSci&Technology, University of Westminster , London, United Kingdom

    Vinood B. Patel

  2. Department of Nutrition and Dietetics,Division of Diabetes and Nutritional Sciences, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Toprak, A.E. (2016). Plasma Growth Arrest-Specific Protein 6 (Gas6) as a Biomarker of Renal Diseases. In: Patel, V., Preedy, V. (eds) Biomarkers in Kidney Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7699-9_37

Download citation

Publish with us

Policies and ethics

Search

Navigation