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Article ; Online: Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Titmuss, E / Milne, K / Jones, M R / Ng, T / Topham, J T / Brown, S D / Schaeffer, D F / Kalloger, S / Wilson, D / Corbett, R D / Williamson, L M / Mungall, K / Mungall, A J / Holt, R A / Nelson, B H / Jones, S J M / Laskin, J / Lim, H J / Marra, M A

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome ... ...

Abstract	Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.
MeSH term(s)	Humans ; Irbesartan/therapeutic use ; Antihypertensive Agents/therapeutic use ; CD8-Positive T-Lymphocytes/pathology ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology
Chemical Substances	Irbesartan (J0E2756Z7N) ; Antihypertensive Agents
Language	English
Publishing date	2023-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065869
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Article ; Online: Targeting the undruggable: immunotherapy meets personalized oncology in the genomic era.

Martin, S D / Coukos, G / Holt, R A / Nelson, B H

Annals of oncology : official journal of the European Society for Medical Oncology

2015 Volume 26, Issue 12, Page(s) 2367–2374

Abstract: Owing to recent advances in genomic technologies, personalized oncology is poised to fundamentally alter cancer therapy. In this paradigm, the mutational and transcriptional profiles of tumors are assessed, and personalized treatments are designed based ... ...

Abstract	Owing to recent advances in genomic technologies, personalized oncology is poised to fundamentally alter cancer therapy. In this paradigm, the mutational and transcriptional profiles of tumors are assessed, and personalized treatments are designed based on the specific molecular abnormalities relevant to each patient's cancer. To date, such approaches have yielded impressive clinical responses in some patients. However, a major limitation of this strategy has also been revealed: the vast majority of tumor mutations are not targetable by current pharmacological approaches. Immunotherapy offers a promising alternative to exploit tumor mutations as targets for clinical intervention. Mutated proteins can give rise to novel antigens (called neoantigens) that are recognized with high specificity by patient T cells. Indeed, neoantigen-specific T cells have been shown to underlie clinical responses to many standard treatments and immunotherapeutic interventions. Moreover, studies in mouse models targeting neoantigens, and early results from clinical trials, have established proof of concept for personalized immunotherapies targeting next-generation sequencing identified neoantigens. Here, we review basic immunological principles related to T-cell recognition of neoantigens, and we examine recent studies that use genomic data to design personalized immunotherapies. We discuss the opportunities and challenges that lie ahead on the road to improving patient outcomes by incorporating immunotherapy into the paradigm of personalized oncology.
MeSH term(s)	Animals ; Cancer Vaccines/administration & dosage ; Genomics/methods ; Genomics/trends ; Humans ; Immunotherapy/methods ; Immunotherapy/trends ; Neoplasms/immunology ; Neoplasms/therapy ; Precision Medicine/methods ; Precision Medicine/trends ; T-Lymphocytes/immunology
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2015-09-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1025984-3
ISSN	1569-8041 ; 0923-7534
ISSN (online)	1569-8041
ISSN	0923-7534
DOI	10.1093/annonc/mdv382
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Article: Phosphatidylinositol 3-kinase potentiates, but does not trigger, T cell proliferation mediated by the IL-2 receptor.

Moon, J J / Nelson, B H

Journal of immunology (Baltimore, Md. : 1950)

2001 Volume 167, Issue 5, Page(s) 2714–2723

Abstract: Proliferative signaling by the IL-2R can occur through two distinct pathways, one mediated by Stat5 and one by the adaptor protein Shc. Although Stat5 induces T cell proliferation by serving as a transcription factor, the mechanism of proliferative ... ...

Abstract	Proliferative signaling by the IL-2R can occur through two distinct pathways, one mediated by Stat5 and one by the adaptor protein Shc. Although Stat5 induces T cell proliferation by serving as a transcription factor, the mechanism of proliferative signaling by Shc is poorly defined. We examined the roles of two major signaling pathways downstream of Shc, the p44/p42 mitogen-activated protein kinase (extracellular signal-related kinase (Erk)) and phosphatidylinositol 3-kinase (PI3K) pathways, in promitogenic gene induction and proliferation in the IL-2-dependent T cell line CTLL-2. Using IL-2R mutants and specific pharmacologic inhibitors, we found that the PI3K, but not Erk, pathway is required for maximal induction of c-myc, cyclin D2, cyclin D3, cyclin E, and bcl-x(L) by Shc. To test whether the PI3K pathway is sufficient for proliferative signaling, a tamoxifen-regulated form of PI3K (mp110ER) was expressed in CTLL-2 cells. Activation of the PI3K pathway through mp110ER failed to up-regulate expression of the c-myc, cyclin D2, cyclin D3, cyclin E, bcl-2, or bcl-x(L) genes or down-regulate expression of p27(Kip1), even when coactivated with the Janus kinases (Jak) or the Raf/Erk pathway. Moreover, mp110ER induced modest levels of thymidine incorporation without subsequent cell division. Although insufficient for mitogenesis, mp110ER enhanced Stat5-mediated proliferative signaling through a mechanism independent of Stat5 transcriptional activity. Thus, in addition to serving a necessary, but insufficient role in Shc-mediated promitogenic gene expression, the PI3K pathway contributes to T cell proliferation by potentiating mitogenic signaling by Stat5.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Adaptor Proteins, Vesicular Transport ; Animals ; Cell Division ; Cell Line ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; Gene Expression ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Lymphocyte Activation ; Mice ; Milk Proteins ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Phosphatidylinositol 3-Kinases/metabolism ; Proteins/metabolism ; Receptors, Interleukin-2/genetics ; Receptors, Interleukin-2/metabolism ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; STAT5 Transcription Factor ; Shc Signaling Adaptor Proteins ; Signal Transduction ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; T-Lymphocytes/cytology ; T-Lymphocytes/enzymology ; T-Lymphocytes/immunology ; Trans-Activators/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Adaptor Proteins, Vesicular Transport ; DNA-Binding Proteins ; Milk Proteins ; Proteins ; Receptors, Interleukin-2 ; Recombinant Fusion Proteins ; STAT5 Transcription Factor ; Shc Signaling Adaptor Proteins ; Shc1 protein, mouse ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; Trans-Activators ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2001-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.167.5.2714
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Article: Biology of the interleukin-2 receptor.

Nelson, B H / Willerford, D M

Advances in immunology

1998 Volume 70, Page(s) 1–81

Abstract: Studies of the biology of the IL-2 receptor have played a major part in establishing several of the fundamental principles that govern our current understanding of immunology. Chief among these is the contribution made by lymphokines to regulation of the ...

Abstract	Studies of the biology of the IL-2 receptor have played a major part in establishing several of the fundamental principles that govern our current understanding of immunology. Chief among these is the contribution made by lymphokines to regulation of the interactions among vast numbers of lymphocytes, comprising a number of functionally distinct lineages. These soluble mediators likely act locally, within the context of the microanatomic organization of the primary and secondary lymphoid organs, where, in combination with signals generated by direct membrane-membrane interactions, a wide spectrum of cell fate decisions is influenced. The properties of IL-2 as a T-cell growth factor spawned the view that IL-2 worked in vivo to promote clonal T-cell expansion during immune responses. Over time, this singular view has suffered from increasing appreciation that the biologic effects of IL-2R signals are much more complex than simply mediating T-cell growth: depending on the set of conditions, IL-2R signals may also promote cell survival, effector function, and apoptosis. These sometimes contradictory effects underscore the fact that a diversity of intracellular signaling pathways are potentially activated by IL-2R. Furthermore, cell fate decisions are based on the integration of multiple signals received by a lymphocyte from the environment; IL-2R signals can thus be regarded as one input to this integration process. In part because IL-2 was first identified as a T-cell growth factor, the major focus of investigation in IL-R2 signaling has been on the mechanism of mitogenic effects in cultured cell lines. Three critical events have been identified in the generation of the IL-2R signal for cell cycle progression, including heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain. These proximal events led to the creation of an activated receptor complex, to which various cytoplasmic signaling molecules are recruited and become substrates for regulatory enzymes (especially tyrosine kinases) that are associated with the receptor. One intriguing outcome of the IL-2R signaling studies performed in cell lines is the apparent functional redundancy of the A and H regions of IL-2R beta, and their corresponding downstream pathways, with respect to the proliferative response. Why should the receptor complex induce cell proliferation through more than one mechanism or pathway? One possibility is that this redundancy is an unusual property of cultured cell lines and that primary lymphocytes require signals from both the A and the H regions of IL-2R beta for optimal proliferative responses in vivo. An alternative possibility is that the A and H regions of IL-2R beta are only redundant with respect to proliferation and that each region plays a unique and essential role in regulating other aspects of lymphocyte physiology. As examples, the A or H region could prove to be important for regulating the sensitivity of lymphocytes to AICD or for promoting the development of NK cells. These issues may be resolved by reconstituting IL-2R beta-/-mice with A-and H-deleted forms of the receptor chain and analyzing the effect on lymphocyte development and function in vivo. In addition to the redundant nature of the A and H regions, there remains a large number of biochemical activities mediated by the IL-2R for which no clear physiological role has been identified. Therefore, the circumstances are ripe for discovering new connections between molecular signaling events activated by the IL-2R and the regulation of immune physiology. Translating biochemical studies of Il-2R function into an understanding of how these signals regulate the immune system has been facilitated by the identification of natural mutations in IL-2R components in humans with immunodeficiency and by the generation of mice with targeted mutations in these gen
MeSH term(s)	Animals ; Cell Differentiation/immunology ; Gene Expression Regulation/immunology ; Humans ; Interleukin-2/physiology ; Lymphocytes/cytology ; Lymphocytes/immunology ; Mice ; Receptors, Interleukin-2/physiology ; Signal Transduction/immunology
Chemical Substances	Interleukin-2 ; Receptors, Interleukin-2
Language	English
Publishing date	1998
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	80226-8
ISSN	1557-8445 ; 0065-2776
ISSN (online)	1557-8445
ISSN	0065-2776
DOI	10.1016/s0065-2776(08)60386-7
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Article ; Online: Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer.

West, N R / Kost, S E / Martin, S D / Milne, K / Deleeuw, R J / Nelson, B H / Watson, P H

British journal of cancer

2012 Volume 108, Issue 1, Page(s) 155–162

Abstract: Background: Regulatory T cells (Tregs) are commonly identified by expression of the transcription factor FOXP3 and are conventionally thought to promote cancer progression by suppressing anti-tumour immune responses. We examined the relationship between ...

Abstract	Background: Regulatory T cells (Tregs) are commonly identified by expression of the transcription factor FOXP3 and are conventionally thought to promote cancer progression by suppressing anti-tumour immune responses. We examined the relationship between FOXP3(+) tumour-infiltrating lymphocytes (TIL) and prognosis in oestrogen receptor (ER)-negative breast cancer, a tumour subtype with poor clinical outcome in which TIL are abundant. Methods: FOXP3(+) and CD8(+) TIL were assessed by immunohistochemistry in a cohort of 175 ER- breast tumours. Results were confirmed in an independent data set of 78 ER- breast tumours with publically available gene expression data. Results: High FOXP3(+) TIL levels were strongly associated with prolonged recurrence-free survival (HR=0.461, P=0.0002), particularly among basal-like tumours (HR=0.280, P=0.0001), for which FOXP3 status was independent of standard prognostic factors. Over 75% of FOXP3(+) TIL in triple negative breast tumours displayed a conventional CD4(+)CD25(+) Treg phenotype. Importantly, FOXP3(+) TIL were positively correlated with CD8(+) (cytotoxic) T cells (r(s)=0.76, P<0.0001), and were prognostically insignificant in tumours with low levels of CD8(+) TIL. These observations were confirmed in an independent cohort. Conclusion: In contrast with current dogma, we show for the first time that FOXP3(+) TIL are associated with robust anti-tumour immunity and favourable prognosis in ER- breast cancer.
MeSH term(s)	Breast Neoplasms/immunology ; Breast Neoplasms/metabolism ; Female ; Forkhead Transcription Factors/metabolism ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Middle Aged ; Prognosis ; T-Lymphocytes, Cytotoxic/immunology ; Tissue Array Analysis
Chemical Substances	FOXP3 protein, human ; Forkhead Transcription Factors
Language	English
Publishing date	2012-11-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/bjc.2012.524
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Article: Substance abuse and the Health Security Act: a case study of a benefit under the Clinton health plan.

Nakken, J M / Nelson, B H

Journal of health and hospital law : a publication of the American Academy of Hospital Attorneys of the American Hospital Association

1994 Volume 27, Issue 2, Page(s) 50–58

MeSH term(s)	Health Care Reform/economics ; Health Care Reform/legislation & jurisprudence ; Humans ; Insurance, Psychiatric/legislation & jurisprudence ; Managed Care Programs/legislation & jurisprudence ; Private Sector ; Public Sector ; Substance Abuse Treatment Centers/economics ; Substance Abuse Treatment Centers/standards ; Substance-Related Disorders/economics ; United States
Language	English
Publishing date	1994-02
Publishing country	United States
Document type	Journal Article
ISSN	1046-4360
ISSN	1046-4360
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Article: Cytoplasmic and cortical determinants interact to specify ectoderm and mesoderm in the leech embryo.

Nelson, B H / Weisblat, D A

Development (Cambridge, England)

1992 Volume 115, Issue 1, Page(s) 103–115

Abstract: In leech embryos, segmental ectoderm and mesoderm are produced by a pair of sister cells located near the animal and vegetal poles, respectively. We have investigated the mechanism that localizes ectodermal and mesodermal fates along the animal-vegetal ... ...

Abstract	In leech embryos, segmental ectoderm and mesoderm are produced by a pair of sister cells located near the animal and vegetal poles, respectively. We have investigated the mechanism that localizes ectodermal and mesodermal fates along the animal-vegetal axis. The results of cleavage arrest and cell ablation experiments suggest that the full range of normal cell interactions are not required for this process. However, when the animal and vegetal hemispheres are separated by re-orientation of the first cleavage plane from meridional to equatorial, the ectodermal fate co-segregates with the animal hemisphere and the mesodermal fate with the vegetal hemisphere. Two pools of yolk-deficient cytoplasm, called teloplasm, are located at the animal and vegetal poles of the zygote, but separation of the animal and vegetal teloplasms is not sufficient for the segregation of ectodermal and mesodermal fates. Rather, complete segregation of fates requires an equatorial cleavage orientation that separates not only the two teloplasms, but also the animal and vegetal cortical regions. This, in conjunction with previous findings, indicates that ectodermal determinants are localized to the cell cortex in the animal hemisphere of the zygote. We propose that these determinants segregate to the ectodermal precursor and interact with factors in teloplasm to transform the fate of this cell from a mesodermal ground state to ectoderm.
MeSH term(s)	Animals ; Cytoplasm/physiology ; Ectoderm/physiology ; Embryonic Induction/physiology ; Leeches/cytology ; Leeches/embryology ; Mesoderm/physiology ; Microscopy, Fluorescence
Language	English
Publishing date	1992-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.115.1.103
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Article: Conversion of ectoderm to mesoderm by cytoplasmic extrusion in leech embryos.

Nelson, B H / Weisblat, D A

Science (New York, N.Y.)

1991 Volume 253, Issue 5018, Page(s) 435–438

Abstract: The role of cytoplasmic domains in the determination of the fates of ectodermal and mesodermal cells has been investigated in leech embryos. When yolk-deficient cytoplasm (teloplasm) was extruded from the animal pole of the zygote, the ectodermal ... ...

Abstract	The role of cytoplasmic domains in the determination of the fates of ectodermal and mesodermal cells has been investigated in leech embryos. When yolk-deficient cytoplasm (teloplasm) was extruded from the animal pole of the zygote, the ectodermal precursor blastomere was converted to a mesodermal fate. This change of fate can be prevented by replacement of the extruded animal teloplasm with teloplasm from the vegetal pole. The fate of the mesodermal precursor blastomere was unaffected by teloplasm extrusion or rearrangement. These results demonstrate that ectodermal and mesodermal determination offate involves a binary decision dependent on the position of teloplasm along the animal-vegetal axis.
Language	English
Publishing date	1991-07-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.253.5018.435
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Article: A leech homolog of twist: evidence for its inheritance as a maternal mRNA.

Soto, J G / Nelson, B H / Weisblat, D A

Gene

1997 Volume 199, Issue 1-2, Page(s) 31–37

Abstract: In the development of leeches such as Helobdella robusta, mesodermal and ectodermal fates segregate to cells DM and DNOPQ, respectively, at fourth cleavage. As one step in identifying genes that may act in mesoderm determination, we have cloned the H. ... ...

Abstract	In the development of leeches such as Helobdella robusta, mesodermal and ectodermal fates segregate to cells DM and DNOPQ, respectively, at fourth cleavage. As one step in identifying genes that may act in mesoderm determination, we have cloned the H. robusta homolog to the Drosophila gene twist. This homolog, designated Hro-twi, exhibits high (> 90%) amino acid identity with other twist-class genes within its basic-helix loop-helix (b-HLH) DNA binding motif and dimerization domain. Like twist, Hro-twi contains CAX-rich stretches: three stretches 5' to the b-HLH and one located 3' of the b-HLH motif. RT-PCR analysis suggests that Hro-twi is present throughout development, beginning as a maternal transcript in the oocyte.
MeSH term(s)	Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; Gene Expression Regulation, Developmental/physiology ; Genes/genetics ; Helix-Loop-Helix Motifs ; Leeches/embryology ; Leeches/genetics ; Molecular Sequence Data ; Nuclear Proteins/genetics ; Oocytes/chemistry ; RNA, Messenger/analysis ; RNA, Messenger/genetics ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Transcription Factors ; Twist-Related Protein 1
Chemical Substances	Nuclear Proteins ; RNA, Messenger ; Transcription Factors ; Twist-Related Protein 1
Language	English
Publishing date	1997-10-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/s0378-1119(97)00327-2
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Article: A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient for Jak kinase activation and induction of proliferation in T cells.

Nelson, B H / Lord, J D / Greenberg, P D

Molecular and cellular biology

1996 Volume 16, Issue 1, Page(s) 309–317

Abstract: The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of ... ...

Abstract	The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of the beta and gamma c chains. To identify the residues of gamma c critical to this process, mutations were introduced into the cytoplasmic domain, and the effects on signalling were analyzed in the IL-2-dependent T-cell line CTLL2 and T-helper clone D10, using chimeric IL-2R chains that bind and are activated by granulocyte-macrophage colony-stimulating factor. Whereas previous studies of fibroblasts and transformed T cells have suggested that signalling by gamma c requires both membrane-proximal and C-terminal subdomains, our results for IL-2-dependent T cells demonstrate that the membrane-proximal 52 amino acids are sufficient to mediate a normal proliferative response, including induction of the proto-oncogenes c-myc and c-fos. Although gamma c is phosphorylated on tyrosine upon receptor activation and could potentially interact with downstream molecules containing SH2 domains, cytoplasmic tyrosine residues were dispensable for mitogenic signalling. However, deletion of a membrane-proximal region conserved among other cytokine receptors (cytoplasmic residues 5 to 37) or an adjacent region unique to gamma c (residues 40 to 52) abrogated functional interaction of the receptor chain with the tyrosine kinase Jak3. This correlated with a loss of all signalling events analyzed, including phosphorylation of the IL-2R beta-associated kinase Jak1, expression of c-myc and c-fos, and induction of the proliferative response. Thus, it appears in T cells that Jak3 is a critical mediator of mitogenic signaling by the gamma c chain.
MeSH term(s)	Amino Acid Sequence ; Animals ; Enzyme Activation ; Genes, fos ; Genes, myc ; Humans ; Janus Kinase 1 ; Janus Kinase 3 ; Ligands ; Lymphocyte Activation ; Mice ; Molecular Sequence Data ; Protein Conformation ; Protein-Tyrosine Kinases/metabolism ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Receptors, Interleukin-2/chemistry ; Receptors, Interleukin-2/genetics ; Receptors, Interleukin-2/metabolism ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Sequence Homology, Amino Acid ; Signal Transduction ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	Ligands ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ; Receptors, Interleukin-2 ; Recombinant Fusion Proteins ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; JAK1 protein, human (EC 2.7.10.2) ; JAK3 protein, human (EC 2.7.10.2) ; Jak1 protein, mouse (EC 2.7.10.2) ; Jak3 protein, mouse (EC 2.7.10.2) ; Janus Kinase 1 (EC 2.7.10.2) ; Janus Kinase 3 (EC 2.7.10.2)
Language	English
Publishing date	1996-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.16.1.309
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In stock of ZB MED Cologne/Königswinter

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Full text online

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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