Plasma membrane rafts and chaperones in cytokine/ STAT signaling.
Languages of publication
We and others have recently obtained data suggesting that cytokine-STAT signaling in many different cell-types is a chaperoned pathway initiated at the level of specialized plasma membrane microdomains called "rafts" (the "raft-STAT signaling hypothesis"). These findings are of broad significance in that all cytokines and growth factors initiate signaling in target cells by interacting with respective cell-surface receptors. The new data suggest that raft microdomains represent the units of function at the cell-surface through which ligand-stimulated STAT signaling is initiated. Moreover, recent evidence shows the involvement of chaperone proteins in regulating the STAT signaling pathway. These chaperones include the human homolog of the tumorous imaginal disc 1 protein (hTid1) which associates with Janus kinase 2 (JAK2) at the level of the plasma membrane, heat shock protein 90 (HSP90) which associates with STAT3 and STAT1 proteins in caveolin-1-containing raft and cytoplasmic complexes, and glucose regulated protein 58 (GRP58/ER-60/ERp57), a thiol dependent protein-disulfide isomerase, found in association with STAT3 "statosome" complexes in the cytosol and in the raft fraction. We suggest a function of the HSP90 chaperone system in preserving IL-6/STAT3 signaling in liver cells in the context of fever. The identification and function of protein partners associated with specific STAT species in rafts and in cytosolic complexes, and in the efficient departure of cytokine-activated STATs from the cytosolic face of rafts towards the cell nucleus are now areas of active investigation.
- Anderson RGW, Jacobsen KA. (2002) A role for lipid shells in targeting proteins to caveolae, rafts and other lipid domains. Science.; 296: 1821-5.
- Bhargava A, Kumar A, Yuan N, Gewitz MH, Mathew R. (1999) Monocrotaline induces interleukin-6 mRNA expression in rat lungs. Heart Disease.; 1: 126-32.
- Bild AH, Turkson J, Jove R. (2002) Cytoplasmic transport of Stat3 by receptor-mediated endocytosis. EMBO J.; 21: 3255-63.
- Brown G, Aitken J, Rixon HW, Sugrue RJ. (2002) Caveolin-1 is incorporated into mature respiratory syncytial virus particles during virus assembly on the surface of virus-infected cells. J Gen Virol.; 83: 611-21.
- Compans RW, Choppin PW. (1973) Orthomyxoviruses and paramyxoviruses. In Ultrastructure of animal viruses and bacteriophages: An Atlas. Dalton AJ, Haguenau F. eds, pp 213-37. Academic Press, New York.
- Cottin V, Doan JES, Riches DWH. (2002) Restricted localization of the TNF receptor CD120a to lipid rafts: a novel role for the death domain. J Immunol.; 168: 4095-102.
- Fleming I, Busse R. (1999) Signal transduction of eNOS activation. Cardiovasc Res.; 43: 532-41.
- Fra AM, Williamson E, Simons K, Parton RG. (1994) Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. J Biol Chem.; 269: 30745-48.
- Galbiati F, Razani B, Lisanti MP. (2001) Emerging themes in lipid rafts and caveolae. Cell.; 106: 403-11.
- Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H. (1987) Interferon β2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A.; 84: 7251-5.
- Guo GG, Bourdi M, Patel K, Kumar V, Fried VA, Pohl LR, Etlinger JD, Sehgal PB. (2002) Association of the chaperone glucose-regulated protein 58 (GRP58/ER-60/ERp57) with STAT3 in the cytosol and plasma membrane complexes. J Interferon Cytokine Res.; 22: 555-63.
- Ju H, Venema VJ, Liang H, Harris MB, Zou R, Venema RC. (2000) Bradykinin activates the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway in vascular endothelial cells: Localization of JAK/STAT signaling proteins in plasmalemmal caveolae. Biochem J.; 351: 257-64.
- Klenk H-D, Choppin PW. (1970a) Lipids of plasma membranes of monkey and hamster kidney cells and of parainfluenza virions grown in these cells. Virology.; 40: 939-47.
- Klenk H-D, Choppin PW. (1970b) Glycosphingolipids of plasma membranes of cultured cells and an enveloped virus (SV5) grown in these cells. Proc Natl Acad Sci U S A.; 66: 57-64.
- Koj A. (1974) Acute phase reactants. The synthesis, turnover and biological significance. In Structure and function of plasma proteins. Allison AC, ed, vol. I, pp 73-125. Plenum Press, New York.
- Kone BC. (2000) Protein-protein interactions controlling nitric oxide synthases. Acta Physiol Scand.; 168: 27-31.
- Koshelnick Y, Ehart M, Hufnagl P, Heinrich PC, Binder BR. (1997) Urokinase receptor is associated with the components of the JAK1/ STAT1 signaling pathway and leads to activation of this pathway upon receptor clustering in the human kidney epithelial tumor cell line TCL-598. J Biol Chem.; 272: 28563-7.
- Kurzchalia TV, Dupree P, Parton RG, Kellner R, Virta H, Lehnert M, Simons K. (1992) VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles. J Cell Biol.; 118: 1003-14.
- Kushner I, Volanakis JE, Gewurz H. (1982) C-reactive protein and the plasma protein response to tissue injury. Ann NY Acad Sci.; 389: 1-482.
- Leon LR. (2002) Cytokine regulation of fever: studies using gene knockout mice. J Appl Physiol.; 92: 2648-55.
- Li S, Couet J, Lisanti MP. (1996) Src tyrosin kinases, G alpha subunits and H-ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the autoactivation of Src tyrosine kinases. J Biol Chem.; 271: 29182-90.
- Lisanti MP, Scherer P, Tang ZL, Sargiacomo M. (1994) Caveolae, caveolin and caveolin-rich membrane domains: a signaling hypothesis. Trends Cell Biol.; 4: 231-5.
- Mackiewicz A, Koj A, Sehgal PB. (1995) Interleukin-6-type cytokines. Ann NY Acad Sci.; 762: 1-522.
- Marmor MD, Julius M. (2001) Role for lipid rafts in regulating interleukin-2 signaling. Blood.; 98: 1489-97.
- Martens AS, Bode JG, Henrich PC, Graeve L. (2000) The cytoplasmic domain of the interleukin-6 receptor gp80 mediates its basolateral sorting in polarized Madin-Darby canine kidney cells. J Cell Sci.; 113: 3593-602.
- Mathew R, Huang J, Shah M, Gewitz MH, Sehgal PB. (2003) Dysregulation of IL-6/caveilin-1/raft/STAT3 function in monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. FASEB J.; 17: A409.
- Muller G, Jung C, Wied S, Welte S, Jordan H, Frick W. (2001) Redistribution of glycolipid raft domain components induces insulin-mimetic signaling in rat adipocytes. Mol Cell Biol.; 21: 4553-67.
- Ndubuisi MI, Guo GG, Fried VA, Etlinger JD, Sehgal PB. (1999) Cellular physiology of STAT3: where's the cytoplasmic monomer? J Biol Chem.; 274: 25499-509.
- Nijsten MWN, de Groot ER, ten Duis HJ, Klasen HJ, Hack CE, Aarden L. (1987) Serum levels of interleukin-6 and acute phase responses. Lancet.; ii(8564): 921.
- Okamoto T, Schlege A, Scherer PE, Lisanti MP. (1998) Caveolins, a family of scaffolding proteins for organizing preassembled signaling complexes at the plasma membrane. J Biol Chem.; 273: 5419-22.
- Podar K, Tai YT, Cole CE, Hideshima T, Sattler M, Hambin A, Mitsiades N, Schlossman R, Davies FE, Morgan GJ, Munshi NC, Chauhan D, Anderson KC. (2003) Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells. J Biol Chem.; 278: 5794-801.
- Rodriguez-Boulan EJ, Sabatini JJ. (1978) Asymmetric budding of viruses in epithelial monolayers: a model system for study of epithelial polarity. Proc Natl Acad Sci U S A.; 75: 5071-5.
- Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RGW. (1992) Caveolin, a protein component of caveolae membrane coats. Cell.; 68: 673-82.
- Sadir R, Lambert A, Lortat-Jacob H, Morel G. (2001) Caveolae and clathrin-coated vesicles: two possible internalization pathways for IFN-gamma and IFN-gamma receptors. Cytokine.; 14: 19-26.
- Sarkar S, Pollack BP, Lin KT, Kotenko SV, Cook JR, Lewis A, Pestka S. (2001) hTid-1, a human DnaJ protein, modulates the interferon signaling pathway. J Biol Chem.; 276: 49034-42.
- Sato N, Yamamoto T, Sekine Y, Yumioka T, Junicho A, Fuse H, Matsuda, T. (2003) Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3. Biochem Biophys Res Commun.; 300: 847-52.
- Schultze AE, Roth RA. (1998) Chronic pulmonary hypertension - the monocrotaline model and involvement of the hemostatic system. J Toxicol Environ Health B Crit Rev.; 1: 271-346.
- Sehgal PB. (2000) STAT signaling through the cytoplasmic compartment: consideration of a new paradigm. Cell Signal.; 12: 525-35.
- Sehgal PB. (2001) Cytokine-induced STAT signaling through the cytoplasmic compartment: further evidence for the statosome model. Adv Exp Med Biol.; 495: 161-8.
- Sehgal PB, Shah M. (2003)Raft-STAT signaling and transcytoplasmic trafficking. In Signal Transducers and Activators of Transcription (STATs): activation and biology. Sehgal PB, Levy D, Hirano T, eds, in press. Kluwer Academic Publishers, New York and Dordrecht.
- Sehgal PB, Grieninger G, Tosato G. (1989) Regulation of the acute phase and immune responses: interleukin-6. Ann NY Acad Sci.; 557: 1-583.
- Sehgal PB, Guo GG, Shah M, Kumar V, Patel K. (2002) Cytokine signaling: STATs in plasma membrane rafts. J Biol Chem.; 277: 12067-74.
- Shah M, Patel K, Fried VA, Sehgal PB. (2002) Interactions of STAT3 with caveolin-1 and heat shock protein 90 in plasma membrane rafts and cytosolic complexes: preservation of cytokine signaling during fever. J Biol Chem.; 277: 45662-9.
- Simons K, Toomre D. (2000) Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol..; 1: 31-41.
- Simons K, Ehehalt R. (2002) Cholesterol, lipid rafts, and disease. J Clin Invest.; 110: 597-603.
- Subramaniam PS, Johnson HM. (2002) Lipid microdomains are required sites for the selective endocytosis and nuclear translocation of IFN-γ, its receptor chain IFN-γ receptor-1, and the phosphorylation and nuclear translocation of STATalpha. J Immunol.; 169: 1959-69.
- Takaoka A, Mitani Y, Suemori H, Sato M, Yokochi T, Noguchi S, Tanaka N, Taniguchi T. (2000) Cross-talk between interferon-γ and -α/β signaling components in caveolar membrane domains. Science.; 288: 2357-60.
- Tillet WS, Francis T. (1930) Serological reactions in pneumonia with a non-protein somatic fraction of the pneumococcus. J Exp Med.; 52: 561-71.
- Zhao YY, Liu Y, Stan RV, Fan L, Gu Y, Dalton N, Chu PH, Peterson K, Ross J, Jr., Chien KR. (2002) Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci U S A.; 99: 11375-80.
Publication order reference