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an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/25 18:28:37」(JST)

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Tyrosine-protein kinase JAK3 is an enzyme that in humans is encoded by the JAK3 gene.^[1]^[2]

Janus kinases

Janus kinase 3 is a tyrosine kinase that belongs to the Janus family of kinases. Other members of the Janus family include JAK1, JAK2 and TYK2. Janus kinases (JAKs) are relatively large kinases of approximately 1150 amino acids with apparent molecular weights of 120-130 kDa.^[3] They are cytosolic tyrosine kinases that are specifically associated with cytokine receptors. Since cytokine receptor proteins lack enzymatic activity, they are dependent upon JAKs to initiate signaling upon binding of their ligands (e.g. cytokines). The cytokine receptors can be divided into five major subgroups based on their different domains and activation motifs. JAK3 is required for signaling of the type I receptors that use the common gamma chain (γc).

**Some cytokine receptors and their involvement with JAK kinases^[4]**
Type	Subgroup	Cytokine Receptor	JAK Kinase
I	homodimeric	EPO, TPO, GH, G-CSF	JAK2
	uses common beta chain (CSF2RΒ)	IL-3, IL-5, GM-CSF	JAK2
	uses gp130 chain	IL-6, IL-11	JAK1, JAK2, Tyk2
	uses common gamma chain (γc)	IL-2, IL-4, IL-7, IL-9, IL-15, IL-21	JAK1, JAK3
II		IFN-α, IFN-β, IFN-γ	JAK1, JAK2, Tyk2

Function

In contrast to the relatively ubiquitous expression of JAK1, JAK2 and Tyk2, JAK3 is predominantly expressed in hematopoietic cells, such as NK cells, T cells and B cells.^[3] JAK3 functions in signal transduction and interacts with members of the STAT (signal transduction and activators of transcription) family. JAK3 is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations that abrogate Janus kinase 3 function cause an autosomal SCID (severe combined immunodeficiency disease).^[5]

Since JAK3 expression is restricted mostly to hematopoietic cells, its role in cytokine signaling is thought to be more restricted than other JAKs. It is most commonly expressed in T cells and NK cells, but has been induced in other leukocytes, including monocytes. JAK3 is involved in signal transduction by receptors that employ the common gamma chain (γc) of the type I cytokine receptor family (e.g. IL-2R, IL-4R, IL-7R, IL-9R, IL-15R, and IL-21R).^[6] Mutations of JAK3 result in severe combined immunodeficiency (SCID). Mice that do not express JAK3 have T-cells and B-cells that fail to respond to many cytokines.^[7]

In addition to its well-known roles in T cells and NK cells, JAK3 has recently been found to mediate IL-8 stimulation in human neutrophils. IL-8 primarily functions to induce chemotaxis in neutrophils and lymphocytes, and JAK3 silencing severely inhibits IL-8-mediated chemotaxis.^[8]

Signal transduction model

Activation of JAK3 by cytokine receptors that contain the common gamma chain (γc)

JAK3 is activated only by cytokines whose receptors contain the common gamma chain (γc) subunit: IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. Cytokine binding induces the association of separate cytokine receptor subunits and the activation of the receptor-associated JAKs. In the absence of cytokine, JAKs lack protein tyrosine kinase activity. Once activated, the JAKs create docking sites for the STAT transcription factors by phosphorylation of specific tyrosine residues on the cytokine receptor subunits. STATs (signal transduction and activators of transcription) are members of a family of transcription factors, and they have src homology 2 (SH2) domains that allow them to bind to these phosphorylated tyrosine residues. After undergoing JAK-mediated phosphorylation, the STAT transcription factors dimerize, translocate to the nucleus, bind DNA at specific elements and induce expression of specific genes.^[3] Cytokine receptors selectively activate particular JAK-STAT pathways to induce transcription of different genes. IL-2 and IL-4 activate JAK1, JAK3 and STAT5.^[9]

Disease relevance

Activating mutations in JAK1, JAK2, and JAK3 have been identified as causes of hematological cancers, while inactivating mutations of JAK3 are known causes of immune deficiency.^[10] Mutations in the common gamma chain (γc) result in X-linked severe combined immunodeficiency (X-SCID). Since γc specifically associates with JAK3, mutations in JAK3 also result in SCID.^[11] Deficiency of JAK3 blocks signaling of the following cytokines and their effects:^[4]

IL-2 - T cell proliferation and maintenance of peripheral tolerance
IL-4 - differentiation of Th2 cells
IL-7 - thymocyte development in the thymus
IL-9 - survival signal for various hematopoietic cells
IL-15 - NK cell development
IL-21 - regulation of immunoglobulin class switching in B cells

Overall, JAK3 deficiency results in the phenotype of SCID characterized by T⁻B⁺NK⁻, which indicates the absence of T cells and NK cells.^[12] Although B cells are present, they are non-functional due to defective B cell activation and impaired antibody class switching.

Since JAK3 is required for immune cell development, targeting JAK3 could be a useful strategy to generate a novel class of immunosuppressant drugs. Moreover, unlike other JAKs, JAK3 is primarily expressed in hematopoietic cells, so a highly specific JAK3 inhibitor should have precise effects on immune cells and minimal pleiotropic defects.^[4] The selectivity of a JAK3 inhibitor would also have advantages over the current widely used immunosuppressant drugs, which have abundant targets and diverse side effects. A JAK3 inhibitor could be useful for treating autoimmune diseases, especially those in which a particular cytokine receptor has a direct role on disease pathogenesis. For example, signaling through the IL-15 receptor is known to be important in the development rheumatoid arthritis,^[13] and the receptors for IL-4 and IL-9 play roles in the development of allergic responses.^[14]

A selective JAK3 inhibitor, designated CP-690550, has been developed and shown promise in clinical trials. This drug has nanomolar potency against JAK3 and was shown to be effective in preventing transplant rejection in a nonhuman primate renal transplant model.^[4] CP-690550 also demonstrated immunosuppressive activity in phase I and II clinical trials of rheumatoid arthritis, psoriasis and organ transplant rejection.^[15] CP-690550 (Tofacitinib) is currently being investigated in phase III clinical trials by Pfizer for the treatment of rheumatoid arthritis.^[16]

Interactions

Janus kinase 3 has been shown to interact with CD247,^[17] TIAF1^[18] and IL2RG.^[19]^[20]

References

^ Riedy MC, Dutra AS, Blake TB, Modi W, Lal BK, Davis J, Bosse A, O'Shea JJ, Johnston JA (February 1997). "Genomic sequence, organization, and chromosomal localization of human JAK3". Genomics 37 (1): 57–61. doi:10.1006/geno.1996.0520. PMID 8921370.
^ Hoffman SM, Lai KS, Tomfohrde J, Bowcock A, Gordon LA, Mohrenweiser HW (September 1997). "JAK3 maps to human chromosome 19p12 within a cluster of proto-oncogenes and transcription factors". Genomics 43 (1): 109–11. doi:10.1006/geno.1997.4792. PMID 9226382.
^ ^a ^b ^c Leonard WJ and O’Shea JJ (1998). "JAKs and STATs: biological implications". Annu. Rev. Immunol. 16: 293–322. doi:10.1146/annurev.immunol.16.1.293. PMID 9597132.
^ ^a ^b ^c ^d O'Shea JJ, Park H, Pesu M, Borie D, Changelian P (2005). "New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway". Curr. Opin. Rheumatol. 17 (3): 305–311. PMID 15838241.
^ "Entrez Gene: JAK3 Janus kinase 3 (a protein tyrosine kinase, leukocyte)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3718.
^ Johnston JA, Kawamura M, Kirken RA, Chen YQ, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ. (1994). "Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2". Nature 370 (6485): 151–153. doi:10.1038/370151a0. PMID 8022485.
^ Fujimoto M, Naka T, Nakagawa R, Kawazoe Y, Morita Y, Tateishi A, Okumura K, Narazaki M, Kishimoto T (2000). "Defective thymocyte development and perturbed homeostasis of T cells in STAT-induced STAT inhibitor-1/suppressors of cytokine signaling-1 transgenic mice". J. Immunol. 165 (4): 1799–806. PMID 10925257.
^ Henkels KM, Frondorf K, Gonzalez-Mejia ME, Doseff AL, Gomez-Cambronero J (2011). "IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3)". FEBS Lett. 585 (1): 159–166. doi:10.1016/j.febslet.2010.11.031. PMC 3021320. PMID 21095188.
^ Witthuhn BA, Silvennoinen O, Miura O, Lai KS, Cwik C, Liu ET, Ihle JN (1994). "Involvement of the Jak-3 Janus kinase in signaling by interleukins 2 and 4 in lymphoid and myeloid cells". Nature 370 (6485): 153–157. doi:10.1038/370153a0. PMID 8022486.
^ Cox L, Cools J (2011). "JAK3 specific kinase inhibitors: when specificity is not enough". Chem. Biol. 18 (3): 277–278. doi:10.1016/j.chembiol.2011.03.002. PMID 21439469.
^ Suzuki K, Nakajima H, Saito Y, Saito T, Leonard WJ, Iwamoto I (2000). "Janus kinase 3 (Jak3) is essential for common cytokine receptor γ chain (γc)-dependent signaling: comparative analysis of γc, Jak3, and γc and Jak3 double-deficient mice". Int. Immunol. 12 (2): 123–132. doi:10.1093/intimm/12.2.123. PMID 10653847.
^ O'Shea JJ, Gadina M, Schreiber RD (2002). "Cytokine signaling in 2002: new surprises in the Jak/Stat pathway". Cell 109 (Suppl): S121–S131. doi:10.1016/S0092-8674(02)00701-8. PMID 11983158.
^ Ferrari-Lacraz S, Zanelli E, Neuberg M, Donskoy E, Kim YS, Zheng XX, Hancock WW, Maslinski W, Li XC, Strom TB, Moll T (2004). "Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein prevents disease development and progression in murine collagen-induced arthritis". J. Immunol. 173 (9): 5818–5826. PMID 15494535.
^ Townsend JM, Fallon GP, Matthews JD, Smith P, Jolin EH, McKenzie NA (2000). "IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development". Immunity 13 (4): 573–583. doi:10.1016/S1074-7613(00)00056-X. PMID 11070175.
^ West K (2009). "CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders". Curr. Opin. Investig. Drugs. 10 (5): 491–504. PMID 19431082.
^ "Long-Term Effectiveness And Safety Of CP-690,550 For The Treatment Of Rheumatoid Arthritis". ClinicalTrials.gov. 29 February 2012. http://www.clinicaltrials.gov/show/NCT00413699. Retrieved 1 March 2012.
^ Tomita K, Saijo K, Yamasaki S, Iida T, Nakatsu F, Arase H, Ohno H, Shirasawa T, Kuriyama T, O'Shea JJ, Saito T (July 2001). "Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and the TCR complex". J. Biol. Chem. 276 (27): 25378–85. doi:10.1074/jbc.M011363200. PMID 11349123.
^ Ji H, Zhai Q, Zhu J, Yan M, Sun L, Liu X, Zheng Z (April 2000). "A novel protein MAJN binds to Jak3 and inhibits apoptosis induced by IL-2 deprival". Biochem. Biophys. Res. Commun. 270 (1): 267–71. doi:10.1006/bbrc.2000.2413. PMID 10733938.
^ Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN (November 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science 266 (5187): 1045–7. doi:10.1126/science.7973659. PMID 7973659.
^ Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O (November 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science 266 (5187): 1042–5. doi:10.1126/science.7973658. PMID 7973658.

External links

Janus Kinase 3 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. JAK3欠損を伴う重度複合型免疫不全（SCID） severe combined immunodeficiency scid with jak3 deficiency
2. 臨床的腎移植における研究中の免疫抑制剤およびそのアプローチ investigational immunosuppressive drugs and approaches in clinical kidney transplantation
3. リウマチ性疾患におけるサイトカインネットワーク：治療の意味 cytokine networks in rheumatic diseases implications for therapy
4. 原発性免疫不全症の診断のためのフローサイトメトリー flow cytometry for the diagnosis of primary immunodeficiencies
5. 重度複合型免疫不全（SCID）：特定の欠損 severe combined immunodeficiency scid specific defects

English Journal

The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (And a surprise discovery: PLD2 is a GEF).

Gomez-Cambronero J.AbstractPhospholipase D (PLD) catalyzes the conversion of the membrane phospholipid phosphatidylcholine to choline and phosphatidic acid (PA). PLD's mission in the cell is two-fold: phospholipid turnover with maintenance of the structural integrity of cellular/intracellular membranes and cell signaling through PA and its metabolites. Precisely, through its product of the reaction, PA, PLD has been implicated in a variety of physiological cellular functions, such as intracellular protein trafficking, cytoskeletal dynamics, chemotaxis of leukocytes and cell proliferation. The catalytic (HKD) and regulatory (PH and PX) domains were studied in detail in the PLD1 isoform, but PLD2 was traditionally studied in lesser detail and much less was known about its regulation. Our laboratory has been focusing on the study of PLD2 regulation in mammalian cells. Over the past few years, we have reported, in regards to the catalytic action of PLD, that PA is a chemoattractant agent that binds to and signals inside the cell through the ribosomal S6 kinases (S6K). Regarding the regulatory domains of PLD2, we have reported the discovery of the PLD2 interaction with Grb2 via Y169 in the PX domain, and further association to Sos, which results in an increase of de novo DNA synthesis and an interaction (also with Grb2) via the adjacent residue Y179, leading to the regulation of cell ruffling, chemotaxis and phagocytosis of leukocytes. We also present the complex regulation by tyrosine phosphorylation by epidermal growth factor receptor (EGF-R), Janus Kinase 3 (JAK3) and Src and the role of phosphatases. Recently, there is evidence supporting a new level of regulation of PLD2 at the PH domain, by the discovery of CRIB domains and a Rac2-PLD2 interaction that leads to a dual (positive and negative) effect on its enzymatic activity. Lastly, we review the surprising finding of PLD2 acting as a GEF. A phospholipase such as PLD that exists already in the cell membrane that acts directly on Rac allows a quick response of the cell without intermediary signaling molecules. This provides only the latest level of PLD2 regulation in a field that promises newer and exciting advances in the next few years.
Cellular signalling.Cell Signal.2011 Dec;23(12):1885-95. Epub 2011 Jun 29.
Phospholipase D (PLD) catalyzes the conversion of the membrane phospholipid phosphatidylcholine to choline and phosphatidic acid (PA). PLD's mission in the cell is two-fold: phospholipid turnover with maintenance of the structural integrity of cellular/intracellular membranes and cell signaling thro
PMID 21740967

A mechanism underlying notch-induced and ubiquitin-mediated Jak3 degradation.

Wu W, Sun XH.SourceOklahoma Medical Research Foundation, United States;
The Journal of biological chemistry.J Biol Chem.2011 Oct 3. [Epub ahead of print]
While Notch signaling is well known to regulate lymphopoiesis, Janus kinase 3 (Jak3) also plays a critical role in promoting lymphocyte development. We have previously found that Notch signaling leads to the degradation of Janus kinase 3 (Jak3) in B lineage cells, suggesting that Notch signaling ex
PMID 21969365

Japanese Journal

JAK2変異体のシグナル伝達解析による真性赤血球増加症発症機構の解明

多胡(船越) めぐみ
YAKUGAKU ZASSHI 131(8), 1183-1187, 2011
It has been well established that disruption of JAK2 signaling regulation is involved in various hematopoietic disorders; however, the detailed mechanism by which abnormal activation of JA …
NAID 130001075906

Effects of Flavonoids on Matrix Metalloproteinase-13 Expression of Interleukin-1β–Treated Articular Chondrocytes and Their Cellular Mechanisms: Inhibition of c-Fos/AP-1 and JAK/STAT Signaling Pathways

Lim Hyun,Park Haeil,Kim Hyun Pyo
Journal of Pharmacological Sciences 116(2), 221-231, 2011
… Apigenin and wogonin primarily inhibit MMP-13 by blocking the c-Fos / activator protein-1 (AP-1) and Janus kinase 2 (JAK2) / signal transducer and activator of transcription 1/2 (STAT1/2) pathways, but not nuclear factor-κB (NF-κB) signaling. …
NAID 130000835867

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関連記事	「kinase」「janus」

「kinase」

Janus kinase 3
	; PDB rendering based on 1yvj.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1YVJ, 3LXK, 3LXL, 3PJC, 4HVD, 4HVG, 4HVH, 4HVI
Identifiers
Symbols	JAK3; JAK-3; JAK3_HUMAN; JAKL; L-JAK; LJAK
External IDs	OMIM: 600173 MGI: 99928 HomoloGene: 181 ChEMBL: 2148 GeneCards: JAK3 Gene
EC number	2.7.10.2
Gene Ontology
Molecular function	• protein tyrosine kinase activity; • non-membrane spanning protein tyrosine kinase activity; • protein binding; • ATP binding;
Cellular component	• cytosol; • cytoskeleton; • endomembrane system; • membrane;
Biological process	• negative regulation of dendritic cell cytokine production; • protein phosphorylation; • enzyme linked receptor protein signaling pathway; • elevation of cytosolic calcium ion concentration; • intracellular protein kinase cascade; • tyrosine phosphorylation of STAT protein; • STAT protein import into nucleus; • peptidyl-tyrosine phosphorylation; • B cell differentiation; • negative regulation of interleukin-10 production; • negative regulation of interleukin-12 production; • interleukin-4-mediated signaling pathway; • positive regulation of activated T cell proliferation; • tyrosine phosphorylation of Stat5 protein; • regulation of apoptotic process; • T cell homeostasis; • negative regulation of apoptotic process; • innate immune response; • negative regulation of FasL biosynthetic process; • negative regulation of T-helper 1 cell differentiation; • positive regulation of transcription from RNA polymerase II promoter; • protein autophosphorylation; • positive regulation of immune response; • negative regulation of T cell activation; • positive regulation of calcium ion transport; • JAK-STAT cascade involved in growth hormone signaling pathway; • regulation of T cell apoptotic process; • negative regulation of thymocyte apoptotic process; • response to interleukin-2; • response to interleukin-4; • response to interleukin-15; • response to interleukin-9;
	Sources: Amigo / QuickGO
Orthologs
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　　[★] キナーゼカイネースリン酸化酵素 phosphoenzyme phosphotransferase 　

「janus」

　　[★]

n.

ヤーヌス、ヤヌス

[pmid8921370-1] Riedy MC, Dutra AS, Blake TB, Modi W, Lal BK, Davis J, Bosse A, O'Shea JJ, Johnston JA (February 1997). "Genomic sequence, organization, and chromosomal localization of human JAK3". Genomics 37 (1): 57–61. doi:10.1006/geno.1996.0520. PMID 8921370.

[pmid9226382-2] Hoffman SM, Lai KS, Tomfohrde J, Bowcock A, Gordon LA, Mohrenweiser HW (September 1997). "JAK3 maps to human chromosome 19p12 within a cluster of proto-oncogenes and transcription factors". Genomics 43 (1): 109–11. doi:10.1006/geno.1997.4792. PMID 9226382.

[pmid9597132-3] Leonard WJ and O’Shea JJ (1998). "JAKs and STATs: biological implications". Annu. Rev. Immunol. 16: 293–322. doi:10.1146/annurev.immunol.16.1.293. PMID 9597132.

[pmid15838241-4] O'Shea JJ, Park H, Pesu M, Borie D, Changelian P (2005). "New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway". Curr. Opin. Rheumatol. 17 (3): 305–311. PMID 15838241.

[5] "Entrez Gene: JAK3 Janus kinase 3 (a protein tyrosine kinase, leukocyte)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3718.

[6] Johnston JA, Kawamura M, Kirken RA, Chen YQ, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ. (1994). "Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2". Nature 370 (6485): 151–153. doi:10.1038/370151a0. PMID 8022485.

[pmid10925257-7] Fujimoto M, Naka T, Nakagawa R, Kawazoe Y, Morita Y, Tateishi A, Okumura K, Narazaki M, Kishimoto T (2000). "Defective thymocyte development and perturbed homeostasis of T cells in STAT-induced STAT inhibitor-1/suppressors of cytokine signaling-1 transgenic mice". J. Immunol. 165 (4): 1799–806. PMID 10925257.

[pmid21095188-8] Henkels KM, Frondorf K, Gonzalez-Mejia ME, Doseff AL, Gomez-Cambronero J (2011). "IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3)". FEBS Lett. 585 (1): 159–166. doi:10.1016/j.febslet.2010.11.031. PMC 3021320. PMID 21095188.

[pmid8022486-9] Witthuhn BA, Silvennoinen O, Miura O, Lai KS, Cwik C, Liu ET, Ihle JN (1994). "Involvement of the Jak-3 Janus kinase in signaling by interleukins 2 and 4 in lymphoid and myeloid cells". Nature 370 (6485): 153–157. doi:10.1038/370153a0. PMID 8022486.

[pmid21439469-10] Cox L, Cools J (2011). "JAK3 specific kinase inhibitors: when specificity is not enough". Chem. Biol. 18 (3): 277–278. doi:10.1016/j.chembiol.2011.03.002. PMID 21439469.

[pmid10653847-11] Suzuki K, Nakajima H, Saito Y, Saito T, Leonard WJ, Iwamoto I (2000). "Janus kinase 3 (Jak3) is essential for common cytokine receptor γ chain (γc)-dependent signaling: comparative analysis of γc, Jak3, and γc and Jak3 double-deficient mice". Int. Immunol. 12 (2): 123–132. doi:10.1093/intimm/12.2.123. PMID 10653847.

[pmid11983158-12] O'Shea JJ, Gadina M, Schreiber RD (2002). "Cytokine signaling in 2002: new surprises in the Jak/Stat pathway". Cell 109 (Suppl): S121–S131. doi:10.1016/S0092-8674(02)00701-8. PMID 11983158.

[pmid15494535-13] Ferrari-Lacraz S, Zanelli E, Neuberg M, Donskoy E, Kim YS, Zheng XX, Hancock WW, Maslinski W, Li XC, Strom TB, Moll T (2004). "Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein prevents disease development and progression in murine collagen-induced arthritis". J. Immunol. 173 (9): 5818–5826. PMID 15494535.

[pmid11070175-14] Townsend JM, Fallon GP, Matthews JD, Smith P, Jolin EH, McKenzie NA (2000). "IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development". Immunity 13 (4): 573–583. doi:10.1016/S1074-7613(00)00056-X. PMID 11070175.

[pmid19431082-15] West K (2009). "CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders". Curr. Opin. Investig. Drugs. 10 (5): 491–504. PMID 19431082.

[16] "Long-Term Effectiveness And Safety Of CP-690,550 For The Treatment Of Rheumatoid Arthritis". ClinicalTrials.gov. 29 February 2012. http://www.clinicaltrials.gov/show/NCT00413699. Retrieved 1 March 2012.

[pmid11349123-17] Tomita K, Saijo K, Yamasaki S, Iida T, Nakatsu F, Arase H, Ohno H, Shirasawa T, Kuriyama T, O'Shea JJ, Saito T (July 2001). "Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and the TCR complex". J. Biol. Chem. 276 (27): 25378–85. doi:10.1074/jbc.M011363200. PMID 11349123.

[pmid10733938-18] Ji H, Zhai Q, Zhu J, Yan M, Sun L, Liu X, Zheng Z (April 2000). "A novel protein MAJN binds to Jak3 and inhibits apoptosis induced by IL-2 deprival". Biochem. Biophys. Res. Commun. 270 (1): 267–71. doi:10.1006/bbrc.2000.2413. PMID 10733938.

[pmid7973659-19] Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN (November 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science 266 (5187): 1045–7. doi:10.1126/science.7973659. PMID 7973659.

[pmid7973658-20] Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O (November 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science 266 (5187): 1042–5. doi:10.1126/science.7973658. PMID 7973658.

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Janus kinase 3