Interleukin-2 receptor function

Cytokine receptors are a group of structurally related receptors, which couple to the JAK-STAT pathway. Cytokine receptors function as homodimers or heterooligomers. They are divided into two main subclasses, class I, which contains receptors for a variety of hematopoietic growth factors and interleukins and class II, which contains receptors for interferons and interleukins 10, 20/24 and 22. 

Venkitaraman, A.R. and Cowling, R.J. (1992). Interleukin 7 receptor functions by recruiting the tyrosine kinase p59fyn through a segment of its cytoplasmic tail. Proc. Natl. Acad. Sci. USA 89, 12083-12087. 

For some cytokine receptors, including the growth hormone receptor and several interleukin receptors, soluble isoforms have been described that comprise all or part of the extracellular domain and may be able to bind the extracellular ligands. By association with other subunits of heterooligomeric receptors, e. g., the gpl30 subunit, these soluble isoforms can function as agonists or antagonists. 

The first report of the action of a chemokine on neurons was published in 1993. The study demonstrated that IL-8 could increase the survival of cultured neurons (Araujo and Cotman, 1993). However, as can be appreciated from its name, IL-8 was not known to be a chemokine at that time and was instead classed as an interleukin. Indeed, the expression of chemokine receptors by neurons was not generally appreciated until around 1997/1998 when several reports suggested this. These reports included observations of the expression of chemokine receptors by neuronal cell lines (Hesselgesser et al. 1997), primary cultures of neurons (Meucci et al. 1998 Ohtani et al. 1998), and in brain sections from HlV-1, Alzheimer s disease, and other patients (Horuk et al. 1997 Westmoreland et al. 1998 Xia et al. 1997). Furthermore, data were obtained, suggesting functions for chemokine signaling in the development of the nervous system (Zou et al. 1998) as well as in neuronal survival and communication (Giovannelli et al. 1998 Meucci et al. 1998). 

BUN, blood urea nitrogen Cl, calcineurin inhibitor CSA, cyclosporine IL-2RA, interleukin 2 receptor antagonist LFTs, liver function tests MMF, mycophenolate mofetil OKT-3, muronomab-CD3 RATG, rabbit antithymocyte immunoglobulin ... 

Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI. Structure and functional expression of a human interleukin-8 receptor. Science 1991 253 1278-1280. 

Damaj BB, McColl SR, Neote K, et al. Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops. FASEB J 1996 10(12) 1426-1434. 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

A series of 3,5-diarylisoxazole and 3,5-diaryl-l,2,4-oxadiazole derivatives, novel classes of small molecule interleukin-8 (IL-8) receptor antagonists, 456 (Ar = 4-FC6H4), have been identified as IL-8 inhibitors. These compounds exhibit activity in an IL-8 binding assay as well as in a functional assay of IL-8 induced... 

In addition to being able to recognize the different cells involved in the acquired immune system of marine mammals, it is important to assure that the cells perform their functions appropriately. The ability of lymphocytes to proliferate upon stimulation (usually with mitogens) has been studied for several decades [1,12,14,15, 32-35], Recent advances include the demonstration of a conserved specificity for standard mitogens used in beluga whales [32] and harbor seals [33], An assay to assess the expression of the receptor for interleukin-2 (IL-2), an early event in lymphocyte activation, was adapted in harbor seals [35], bottlenose dolphins [36], and sea otters [37], Molecular and biochemical mechanisms of activation of beluga T lymphocytes do not vary substantially from those in other mammals [38],... 

Interleukins Interleukins are proteins produced mainly by leukocytes. There are many interleukins within this family (Table 4.4). Interleukins have a number of functions but are principally involved in mediating and directing immune cells to proliferate and differentiate. Each interleukin binds to a specific receptor and produces its response. 

Diveu C, Venereau E, Froger J, et al Molecular and functional characterization of a soluble form of oncostatin M/interleukin-31 shared receptor. J Biol Chem 2006 281 36673-36682. Stress C, Radtke S, Clahsen T, et al Oncostatin M receptor-mediated signal transduction is negatively regulated by SOCS3 through a receptor tyrosine-independent mechanism. J Biol Chem 2006 281 8458-8468. 

Cytokines are proteins that serve as signal molecules in cell-cell communication, and as such, perform a central and very diverse function in growth and differentiation of an organism. Representatives of cytokines control proliferation, differentiation and function of cells of the immune system and of cells of the blood-forming system. Furthermore, they are involved in processes of inflammation and in the neuronal, hema-poetic and embryonal development of the organism. Known cytokines include the interleukins (IL), erythropoietin, growth hormone, interferons (INF) and tumor necrosis factor (TNF) (see Table 8.1). A review of cytokines and cytokine receptors is to be found in HiU and Treisman, (1995) Taniguchi et al., (1995) and Moutoussamy et al., (1998). 

Dr. Alain Fisher and his research team have successfully treated two infants with XSCIDS, a severe form of SCIDS that occurs only in boys. These patients lack functional T cells and natural killer cells (NK) due to mutations in the % chain of the cytokine receptor family that recognizes interleukins (i.e., IL-2, -4, -7, -9, and -15). Ex vivo gene transfer was employed. The researchers delivered the wild-type sequence for the yc chain cytokine receptor subunit to hematopoietic stem cells isolated from these patients using a nonreplicating murine retrovirus [14,15]. 

Hacein-Bey, H., M. Cavazzana-Calvo, F. Le Deist, A. Dautry-Varsat, C. Hivroz, I. Riviere, O. Danes, J.M. Heard, K. Sugamura, A. Fischer, and G. De Saint Basile, gamma-c gene transfer into SCID XI patients B-cell lines restores normal high-affinity interleukin-2 receptor expression and function. Blood, 1996. 87(8) 3108-16. 

Through regulation of gene transcription, cyclosporine inhibits interleukin-1 and interleukin-2 receptor production and secondarily inhibits macrophage-T-cell interaction and T-cell responsiveness (see Chapter 55). T-cell-dependent -cell function is also affected. 

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