Robert Kirken
Title Dean College of Science and PI RCMI Grant
Faculty Rank Professor
Degree Ph.D.
Institution University of Texas at El Paso
Department Biological Sciences
Clusters Cancer
Address
University of Texas at El Paso
500 W. University
Bioscience Research Building
City El Paso
State TX
Postal Code 79968
Telephone (915) 747- 5536
Fax
Email
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Narrative


The goal of the laboratory is to understand the intracellular signaling pathways responsible for mediating T cell activation so that rational strategies to regulate immune responses can be achieved. To accomplish this objective it is necessary to first understand the mechanisms through which these cells are activated. It is clear that T cell activation requires engagement with antigen, costimulatory molecules, and intercellular signaling peptides called cytokines. One cytokine we are particularly interested in is interleukin 2 (IL2). IL2 belongs to a family of cytokines that utilize a shared receptor subunit referred to as the IL2 receptor common gamma (g) chain, or gc. This receptor is recruited by one of several cytokines, which then activate a select member of the Janus tyrosine Kinase (JAK) family, JAK3. JAK3 plays a key role in the development and function of T cells. However, the intracellular molecules activated by JAK3 are not readily known nor the genes it regulates. Therefore, the laboratory is focused on identifying and characterizing these signaling proteins to better understand this event. We are particularly interested in a family of gene regulating molecules known as signal transducers and activators of transcription (Stats) and several ongoing studies in the laboratory are examining the role that Stat5a and Stat5b perform in regulating T cell activity and disease. Through critical analysis of these signaling pathways it will be possible to utilize pharmaceuticals to manipulate these secondary messengers and subsequently modulate an immune response. Ultimately, these studies will enable us to develop novel immunomodulatory drugs with therapeutic potential against important clinical conditions such as cancer, graft-versus-host disease, allergy, and autoimmune disorders

Publications

1. Fu G, Sanjay ST, Zhou W, Brekken RA, Kirken RA, Li X. Exploration of Nanoparticle-Mediated Photothermal Effect of TMB-H2O2 Colorimetric System and Its Application in a Visual Quantitative Photothermal Immunoassay. Anal Chem. 2018 May 01; 90(9):5930-5937.
  View in: PubMed (29641893)
 
2. Ross JA, Robles-Escajeda E, Oaxaca DM, Padilla DL, Kirken RA. The prohibitin protein complex promotes mitochondrial stabilization and cell survival in hematologic malignancies. Oncotarget. 2017 Sep 12; 8(39):65445-65456.
  View in: PubMed (29029444)
 
3. Parra K, Valenzuela P, Lerma N, Gallegos A, Reza LC, Rodriguez G, Emmenegger U, Di Desidero T, Bocci G, Felder MS, Manciu M, Kirken RA, Francia G. Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth. Br J Cancer. 2017 Jan; 116(3):324-334.
  View in: PubMed (28056464)
 
4. Oaxaca DM, Yang-Reid SA, Ross JA, Rodriguez G, Staniswalis JG, Kirken RA. Sensitivity of imatinib-resistant T315I BCR-ABL CML to a synergistic combination of ponatinib and forskolin treatment. Tumour Biol. 2016 Sep; 37(9):12643-12654.
  View in: PubMed (27444277)
 
5. Martinez GS, Ross JA, Kirken RA. Transforming Mutations of Jak3 (A573V and M511I) Show Differential Sensitivity to Selective Jak3 Inhibitors. Clin Cancer Drugs. 2016; 3(2):131-137.
  View in: PubMed (29046866)
 
6. Ruiz-Medina BE, Ross JA, Kirken RA. Interleukin-2 Receptor ß Thr-450 Phosphorylation Is a Positive Regulator for Receptor Complex Stability and Activation of Signaling Molecules. J Biol Chem. 2015 Aug 21; 290(34):20972-83.
  View in: PubMed (26152718)
 
7. Gonzalez H, Lema C, Kirken RA, Maldonado RA, Varela-Ramirez A, Aguilera RJ. Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway. Clin Cancer Drugs. 2015; 2(2):138-147.
  View in: PubMed (27054085)
 
8. Ross JA, Spadaro M, Rosado DC, Cavallo F, Kirken RA, Pericle F. Inhibition of JAK3 with a novel, selective and orally active small molecule induces therapeutic response in T-cell malignancies. Leukemia. 2014 Apr; 28(4):941-4.
  View in: PubMed (24153015)
 
9. Robles-Escajeda E, Lerma D, Nyakeriga AM, Ross JA, Kirken RA, Aguilera RJ, Varela-Ramirez A. Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells. PLoS One. 2013; 8(9):e73508.
  View in: PubMed (24039967)
 
10. Nagy ZS, Ross JA, Rodriguez G, Balint BL, Szeles L, Nagy L, Kirken RA. Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells. PLoS One. 2013; 8(2):e57326.
  View in: PubMed (23451206)
 
11. Rodriguez G, Ross JA, Nagy ZS, Kirken RA. Forskolin-inducible cAMP pathway negatively regulates T-cell proliferation by uncoupling the interleukin-2 receptor complex. J Biol Chem. 2013 Mar 08; 288(10):7137-46.
  View in: PubMed (23341462)
 
12. Ross JA, Rodriguez G, Kirken RA. Analysis of Janus tyrosine kinase phosphorylation and activation. Methods Mol Biol. 2013; 967:3-20.
  View in: PubMed (23296718)
 
13. Mitra A, Ross JA, Rodriguez G, Nagy ZS, Wilson HL, Kirken RA. Signal transducer and activator of transcription 5b (Stat5b) serine 193 is a novel cytokine-induced phospho-regulatory site that is constitutively activated in primary hematopoietic malignancies. J Biol Chem. 2012 May 11; 287(20):16596-608.
  View in: PubMed (22442148)
 
14. Nagy ZS, Ross JA, Rodriguez G, Bader J, Dimmock J, Kirken RA. Uncoupling JAK3 activation induces apoptosis in human lymphoid cancer cells via regulating critical survival pathways. FEBS Lett. 2010 Apr 16; 584(8):1515-20.
  View in: PubMed (20211620)
 
15. Ross JA, Cheng H, Nagy ZS, Frost JA, Kirken RA. Protein phosphatase 2A regulates interleukin-2 receptor complex formation and JAK3/STAT5 activation. J Biol Chem. 2010 Feb 05; 285(6):3582-91.
  View in: PubMed (19923221)
 
16. Nagy ZS, LeBaron MJ, Ross JA, Mitra A, Rui H, Kirken RA. STAT5 regulation of BCL10 parallels constitutive NFkappaB activation in lymphoid tumor cells. Mol Cancer. 2009 Aug 26; 8:67.
  View in: PubMed (19709433)
 
17. Stepkowski SM, Chen W, Ross JA, Nagy ZS, Kirken RA. STAT3: an important regulator of multiple cytokine functions. Transplantation. 2008 May 27; 85(10):1372-7.
  View in: PubMed (18497672)
 
18. Dagvadorj A, Kirken RA, Leiby B, Karras J, Nevalainen MT. Transcription factor signal transducer and activator of transcription 5 promotes growth of human prostate cancer cells in vivo. Clin Cancer Res. 2008 Mar 01; 14(5):1317-24.
  View in: PubMed (18316550)
 
19. Cheng H, Ross JA, Frost JA, Kirken RA. Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity. Mol Cell Biol. 2008 Apr; 28(7):2271-82.
  View in: PubMed (18250158)
 
20. Tan SH, Dagvadorj A, Shen F, Gu L, Liao Z, Abdulghani J, Zhang Y, Gelmann EP, Zellweger T, Culig Z, Visakorpi T, Bubendorf L, Kirken RA, Karras J, Nevalainen MT. Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells. Cancer Res. 2008 Jan 01; 68(1):236-48.
  View in: PubMed (18172316)
 
21. Ross JA, Nagy ZS, Kirken RA. The PHB1/2 phosphocomplex is required for mitochondrial homeostasis and survival of human T cells. J Biol Chem. 2008 Feb 22; 283(8):4699-713.
  View in: PubMed (18086671)
 
22. Ross JA, Nagy ZS, Cheng H, Stepkowski SM, Kirken RA. Regulation of T cell homeostasis by JAKs and STATs. Arch Immunol Ther Exp (Warsz). 2007 Jul-Aug; 55(4):231-45.
  View in: PubMed (17659375)
 
23. Neilson LM, Zhu J, Xie J, Malabarba MG, Sakamoto K, Wagner KU, Kirken RA, Rui H. Coactivation of janus tyrosine kinase (Jak)1 positively modulates prolactin-Jak2 signaling in breast cancer: recruitment of ERK and signal transducer and activator of transcription (Stat)3 and enhancement of Akt and Stat5a/b pathways. Mol Endocrinol. 2007 Sep; 21(9):2218-32.
  View in: PubMed (17550976)
 
24. Nagy ZS, Rui H, Stepkowski SM, Karras J, Kirken RA. A preferential role for STAT5, not constitutively active STAT3, in promoting survival of a human lymphoid tumor. J Immunol. 2006 Oct 15; 177(8):5032-40.
  View in: PubMed (17015686)
 
25. Stepkowski SM, Kirken RA. Janus tyrosine kinases and signal transducers and activators of transcription regulate critical functions of T cells in allograft rejection and transplantation tolerance. Transplantation. 2006 Aug 15; 82(3):295-303.
  View in: PubMed (16906023)
 
26. Qiu L, Lai R, Lin Q, Lau E, Thomazy DM, Calame D, Ford RJ, Kwak LW, Kirken RA, Amin HM. Autocrine release of interleukin-9 promotes Jak3-dependent survival of ALK+ anaplastic large-cell lymphoma cells. Blood. 2006 Oct 01; 108(7):2407-15.
  View in: PubMed (16763206)
 
27. Zhang Y, Kirken RA, Furian L, Janczewska S, Qu X, Hancock WW, Wang M, Tejpal N, Kerman R, Kahan BD, Stepkowski SM. Allograft rejection requires STAT5a/b-regulated antiapoptotic activity in T cells but not B cells. J Immunol. 2006 Jan 01; 176(1):128-37.
  View in: PubMed (16365403)
 
28. Stepkowski SM, Kao J, Wang ME, Tejpal N, Podder H, Furian L, Dimmock J, Jha A, Das U, Kahan BD, Kirken RA. The Mannich base NC1153 promotes long-term allograft survival and spares the recipient from multiple toxicities. J Immunol. 2005 Oct 01; 175(7):4236-46.
  View in: PubMed (16177063)
 
29. Stepkowski SM, Kirken RA. Unique advantage of Janus kinase 3 as a target for selective and nontoxic immunosuppression. Expert Rev Clin Immunol. 2005 Sep; 1(3):307-10.
  View in: PubMed (20476981)
 
30. Langer R, Wang M, Stepkowski SM, Hancock WW, Han R, Li P, Feng L, Kirken RA, Berens KL, Dupre B, Podder H, Dixon RA, Kahan BD. Selectin inhibitor bimosiamose prolongs survival of kidney allografts by reduction in intragraft production of cytokines and chemokines. J Am Soc Nephrol. 2004 Nov; 15(11):2893-901.
  View in: PubMed (15504942)
 
31. Wang Y, Malabarba MG, Nagy ZS, Kirken RA. Interleukin 4 regulates phosphorylation of serine 756 in the transactivation domain of Stat6. Roles for multiple phosphorylation sites and Stat6 function. J Biol Chem. 2004 Jun 11; 279(24):25196-203.
  View in: PubMed (15069079)
 
32. Nagy ZS, Ross J, Cheng H, Stepkowski SM, Kirken RA. Regulation of lymphoid cell apoptosis by Jaks and Stats. Crit Rev Immunol. 2004; 24(2):87-110.
  View in: PubMed (15581392)
 
33. Behbod F, Nagy ZS, Stepkowski SM, Karras J, Johnson CR, Jarvis WD, Kirken RA. Specific inhibition of Stat5a/b promotes apoptosis of IL-2-responsive primary and tumor-derived lymphoid cells. J Immunol. 2003 Oct 15; 171(8):3919-27.
  View in: PubMed (14530308)
 
34. Kahan BD, Kirken RA, Stepkowski SM. New approaches to transplant immunosuppression. Transplant Proc. 2003 Aug; 35(5):1621-3.
  View in: PubMed (12962733)
 
35. Kirken RA, Wang YL. Molecular actions of sirolimus: sirolimus and mTor. Transplant Proc. 2003 May; 35(3 Suppl):227S-230S.
  View in: PubMed (12742500)
 
36. Nagy ZS, Wang Y, Erwin-Cohen RA, Aradi J, Monia B, Wang LH, Stepkowski SM, Rui H, Kirken RA. Interleukin-2 family cytokines stimulate phosphorylation of the Pro-Ser-Pro motif of Stat5 transcription factors in human T cells: resistance to suppression of multiple serine kinase pathways. J Leukoc Biol. 2002 Oct; 72(4):819-28.
  View in: PubMed (12377952)
 
37. Stepkowski SM, Kirken RA, Trawick BW, Wang M, Tejpal N, Wang ME, Tian L, Clark J, Kahan BD. Allochimeric class I MHC protein-induced tolerance by partial TCR engagement requires activation of both CTL4- and common gamma-chain-dependent cytokine signals. Transplantation. 2002 Apr 27; 73(8):1227-35.
  View in: PubMed (11981413)
 
38. Stepkowski SM, Erwin-Cohen RA, Behbod F, Wang ME, Qu X, Tejpal N, Nagy ZS, Kahan BD, Kirken RA. Selective inhibitor of Janus tyrosine kinase 3, PNU156804, prolongs allograft survival and acts synergistically with cyclosporine but additively with rapamycin. Blood. 2002 Jan 15; 99(2):680-9.
  View in: PubMed (11781254)
 
39. Kirken RA. Targeting Jak3 for immune suppression and allograft acceptance. Transplant Proc. 2001 Nov-Dec; 33(7-8):3268-70.
  View in: PubMed (11750399)
 
40. Stepkowski SM, Nagy ZS, Wang ME, Behbod F, Erwin-Cohen R, Kahan BD, Kirken RA. PNU156804 inhibits Jak3 tyrosine kinase and rat heart allograft rejection. Transplant Proc. 2001 Nov-Dec; 33(7-8):3272-3.
  View in: PubMed (11750401)
 
41. Stepkowski SM, Nagy ZS, Kahan BD, Kirken RA. The role of signals 1, 2, and 3 in induction of transplantation tolerance. Transplant Proc. 2001 Nov-Dec; 33(7-8):3831-2.
  View in: PubMed (11750632)
 
42. Stepkowski SM, Kirken RA, Nagy ZS, Trawick BW, Wang M, Tejpal N, Wang ME, Tian L, Clark J, Kahan BD. The role of Stat5 in the induction of regulatory T cells in transplantation tolerance. Transplant Proc. 2001 Nov-Dec; 33(7-8):3835-6.
  View in: PubMed (11750634)
 
43. Yamashita H, Nevalainen MT, Xu J, LeBaron MJ, Wagner KU, Erwin RA, Harmon JM, Hennighausen L, Kirken RA, Rui H. Role of serine phosphorylation of Stat5a in prolactin-stimulated beta-casein gene expression. Mol Cell Endocrinol. 2001 Oct 25; 183(1-2):151-63.
  View in: PubMed (11604235)
 
44. Qu X, Kirken RA, Tian L, Wang M, Bennett CF, Stepkowski SM. Selective inhibition of IL-2 gene expression by IL-2 antisense oligonucleotides blocks heart allograft rejection. Transplantation. 2001 Sep 15; 72(5):915-23.
  View in: PubMed (11571459)
 
45. Behbod F, Erwin-Cohen RA, Wang ME, Trawick BW, Qu X, Verani R, Kahan BD, Stepkowski SM, Kirken RA. Concomitant inhibition of Janus kinase 3 and calcineurin-dependent signaling pathways synergistically prolongs the survival of rat heart allografts. J Immunol. 2001 Mar 15; 166(6):3724-32.
  View in: PubMed (11238613)
 
46. Kirken RA, Erwin-Cohen R, Behbod F, Wang M, Stepkowski SM, Kahan BD. Tyrphostin AG490 selectively inhibits activation of the JAK3/STAT5/MAPK pathway and rejection of rat heart allografts. Transplant Proc. 2001 Feb-Mar; 33(1-2):95.
  View in: PubMed (11266723)
 
47. Stepkowski SM, Kirken RA, Wang M, Yu J, Akioka K, Kahan BD. Tolerance induction by alteration of T cell receptor (TCR) signaling using an allochimeric donor/recipient class I MHC protein. Transplant Proc. 2001 Feb-Mar; 33(1-2):131.
  View in: PubMed (11266741)
 
48. Wang M, Kirken R, Behbod F, Erwin-Cohen R, Stepkowski SM, Kahan BD. Inhibition of Jak3 tyrosine kinase by PNU156804 blocks rat heart allograft rejection. Transplant Proc. 2001 Feb-Mar; 33(1-2):201.
  View in: PubMed (11266779)
 
49. Tian L, Qu X, Wang ME, Kirken RA, Bennett FC, Stepkowski SM. Selective inhibition of IL-2 mRNA blocks allograft rejection by limiting T cell clonal expansion. Transplant Proc. 2001 Feb-Mar; 33(1-2):330.
  View in: PubMed (11266845)
 
50. Yen CH, Yang YC, Ruscetti SK, Kirken RA, Dai RM, Li CC. Involvement of the ubiquitin-proteasome pathway in the degradation of nontyrosine kinase-type cytokine receptors of IL-9, IL-2, and erythropoietin. J Immunol. 2000 Dec 01; 165(11):6372-80.
  View in: PubMed (11086075)
 
51. Kirken RA, Erwin RA, Wang L, Wang Y, Rui H, Farrar WL. Functional uncoupling of the Janus kinase 3-Stat5 pathway in malignant growth of human T cell leukemia virus type 1-transformed human T cells. J Immunol. 2000 Nov 01; 165(9):5097-104.
  View in: PubMed (11046040)
 
52. Stepkowski SM, Kirken RA. The role of IL-2 in allograft rejection--a lesson learned from experimental work. Transplantation. 2000 Jun 27; 69(12):2480-2.
  View in: PubMed (10910265)
 
53. Wang LH, Kirken RA, Yang XY, Erwin RA, DaSilva L, Yu CR, Farrar WL. Selective disruption of interleukin 4 autocrine-regulated loop by a tyrosine kinase inhibitor restricts activity of T-helper 2 cells. Blood. 2000 Jun 15; 95(12):3816-22.
  View in: PubMed (10845915)
 
54. Wang LH, Yang XY, Kirken RA, Resau JH, Farrar WL. Targeted disruption of stat6 DNA binding activity by an oligonucleotide decoy blocks IL-4-driven T(H)2 cell response. Blood. 2000 Feb 15; 95(4):1249-57.
  View in: PubMed (10666197)
 
55. Kirken RA, Erwin RA, Taub D, Murphy WJ, Behbod F, Wang L, Pericle F, Farrar WL. Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells. J Leukoc Biol. 1999 Jun; 65(6):891-9.
  View in: PubMed (10380915)
 
56. Wang LH, Kirken RA, Erwin RA, Yu CR, Farrar WL. JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the tyrphostin AG-490 regulation of IL-2-mediated T cell response. J Immunol. 1999 Apr 01; 162(7):3897-904.
  View in: PubMed (10201908)
 
57. Yamashita H, Xu J, Erwin RA, Farrar WL, Kirken RA, Rui H. Differential control of the phosphorylation state of proline-juxtaposed serine residues Ser725 of Stat5a and Ser730 of Stat5b in prolactin-sensitive cells. J Biol Chem. 1998 Nov 13; 273(46):30218-24.
  View in: PubMed (9804779)
 
58. DaSilva L, Kirken RA, Taub DD, Evans GA, Duhé RJ, Bailey MA, Farrar WL. Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family. Gene. 1998 Oct 09; 221(1):135-42.
  View in: PubMed (9852958)
 
59. Yu CR, Kirken RA, Malabarba MG, Young HA, Ortaldo JR. Differential regulation of the Janus kinase-STAT pathway and biologic function of IL-13 in primary human NK and T cells: a comparative study with IL-4. J Immunol. 1998 Jul 01; 161(1):218-27.
  View in: PubMed (9647227)
 
60. Kirken RA, Evans GA, Duhé RJ, DaSilva L, Malabarba MG, Erwin RA, Farrar WL. Mechanisms of cytokine signal transduction: IL-2, IL-4 and prolactin as hematopoietin receptor models. Vet Immunol Immunopathol. 1998 May 15; 63(1-2):27-36.
  View in: PubMed (9656438)
 
61. Duhé RJ, Evans GA, Erwin RA, Kirken RA, Cox GW, Farrar WL. Nitric oxide and thiol redox regulation of Janus kinase activity. Proc Natl Acad Sci U S A. 1998 Jan 06; 95(1):126-31.
  View in: PubMed (9419340)
 
62. Pericle F, Pinto LA, Hicks S, Kirken RA, Sconocchia G, Rusnak J, Dolan MJ, Shearer GM, Segal DM. HIV-1 infection induces a selective reduction in STAT5 protein expression. J Immunol. 1998 Jan 01; 160(1):28-31.
  View in: PubMed (9551952)
 
63. Pericle F, Kirken RA, Bronte V, Sconocchia G, DaSilva L, Segal DM. Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes. J Immunol. 1997 Sep 15; 159(6):2580-5.
  View in: PubMed (9300676)
 
64. Curiel RE, Lahesmaa R, Subleski J, Cippitelli M, Kirken RA, Young HA, Ghosh P. Identification of a Stat-6-responsive element in the promoter of the human interleukin-4 gene. Eur J Immunol. 1997 Aug; 27(8):1982-7.
  View in: PubMed (9295035)
 
65. Kirken RA, Malabarba MG, Xu J, DaSilva L, Erwin RA, Liu X, Hennighausen L, Rui H, Farrar WL. Two discrete regions of interleukin-2 (IL2) receptor beta independently mediate IL2 activation of a PD98059/rapamycin/wortmannin-insensitive Stat5a/b serine kinase. J Biol Chem. 1997 Jun 13; 272(24):15459-65.
  View in: PubMed (9182578)
 
66. Kirken RA, Malabarba MG, Xu J, Liu X, Farrar WL, Hennighausen L, Larner AC, Grimley PM, Rui H. Prolactin stimulates serine/tyrosine phosphorylation and formation of heterocomplexes of multiple Stat5 isoforms in Nb2 lymphocytes. J Biol Chem. 1997 May 30; 272(22):14098-103.
  View in: PubMed (9162035)
 
67. Malabarba MG, Rui H, Deutsch HH, Chung J, Kalthoff FS, Farrar WL, Kirken RA. Interleukin-13 is a potent activator of JAK3 and STAT6 in cells expressing interleukin-2 receptor-gamma and interleukin-4 receptor-alpha. Biochem J. 1996 Nov 01; 319 ( Pt 3):865-72.
  View in: PubMed (8920992)
 
68. Pericle F, Kirken RA, Epling-Burnette PK, Blanchard DK, Djeu JY. Direct killing of interleukin-2-transfected tumor cells by human neutrophils. Int J Cancer. 1996 May 03; 66(3):367-73.
  View in: PubMed (8621259)
 
69. DaSilva L, Rui H, Erwin RA, Howard OM, Kirken RA, Malabarba MG, Hackett RH, Larner AC, Farrar WL. Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor tyrosines TYR402, TYR479, TYR515 and TYR580. Mol Cell Endocrinol. 1996 Mar 25; 117(2):131-40.
  View in: PubMed (8737372)
 
70. Kirken RA, Lincoln AJ, Fink PS, Prochaska LJ. High yield purification of a four subunit caa3-type cytochrome oxidase from the thermophilic bacterium Bacillus PS3 using fast protein liquid chromatography. Protein Expr Purif. 1995 Oct; 6(5):707-15.
  View in: PubMed (8535166)
 
71. Kirken RA, Rui H, Malabarba MG, Howard OM, Kawamura M, O'Shea JJ, Farrar WL. Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain. Cytokine. 1995 Oct; 7(7):689-700.
  View in: PubMed (8580378)
 
72. Erwin RA, Kirken RA, Malabarba MG, Farrar WL, Rui H. Prolactin activates Ras via signaling proteins SHC, growth factor receptor bound 2, and son of sevenless. Endocrinology. 1995 Aug; 136(8):3512-8.
  View in: PubMed (7628388)
 
73. Malabarba MG, Kirken RA, Rui H, Koettnitz K, Kawamura M, O'Shea JJ, Kalthoff FS, Farrar WL. Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alpha. J Biol Chem. 1995 Apr 21; 270(16):9630-7.
  View in: PubMed (7721895)
 
74. Howard OM, Kirken RA, Garcia GG, Hackett RH, Farrar WL. Structural domains of interleukin-2 receptor beta critical for signal transduction: kinase association and nuclear complex-formation. Biochem J. 1995 Feb 15; 306 ( Pt 1):217-24.
  View in: PubMed (7532397)
 
75. Rui H, Lebrun JJ, Kirken RA, Kelly PA, Farrar WL. JAK2 activation and cell proliferation induced by antibody-mediated prolactin receptor dimerization. Endocrinology. 1994 Oct; 135(4):1299-306.
  View in: PubMed (7925093)
 
76. Kirken RA, Rui H, Malabarba MG, Farrar WL. Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel leukocyte-specific Janus kinase. J Biol Chem. 1994 Jul 22; 269(29):19136-41.
  View in: PubMed (7518451)
 
77. DaSilva L, Howard OM, Rui H, Kirken RA, Farrar WL. Growth signaling and JAK2 association mediated by membrane-proximal cytoplasmic regions of prolactin receptors. J Biol Chem. 1994 Jul 15; 269(28):18267-70.
  View in: PubMed (8034567)
 
78. Johnston JA, Kawamura M, Kirken RA, Chen YQ, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ. Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. Nature. 1994 Jul 14; 370(6485):151-3.
  View in: PubMed (8022485)
 
79. Rui H, Kirken RA, Farrar WL. Activation of receptor-associated tyrosine kinase JAK2 by prolactin. J Biol Chem. 1994 Feb 18; 269(7):5364-8.
  View in: PubMed (7508935)
 
80. Kirken RA, Rui H, Howard OM, Farrar WL. Involvement of JAK-family tyrosine kinases in hematopoietin receptor signal transduction. Prog Growth Factor Res. 1994; 5(2):195-211.
  View in: PubMed (7919224)
 
81. Kirken RA, Rui H, Evans GA, Farrar WL. Characterization of an interleukin-2 (IL-2)-induced tyrosine phosphorylated 116-kDa protein associated with the IL-2 receptor beta-subunit. J Biol Chem. 1993 Oct 25; 268(30):22765-70.
  View in: PubMed (7693677)