Abstract
SHP-1 is a key tyrosine phosphatase that acts as a negative regulator of signal transduction in lymphocytes, which has been found down-regulated in several T cell lines derived from human T cell malignancies. The standardization of a sensitive ELISA for the quantification of SHP-1 protein in peripheral T and B lymphocytes has enabled us to quantify the SHP-1 content of freshly isolated T cells from patients with Sezary syndrome and in the Sezary T cell line HUT-78. In all cases, a dramatic decrease in the content of this protein, when compared with the content in healthy volunteer controls, was observed. These results were corroborated when the expression of SHP-1 mRNA was analyzed. In order to study whether there was any correlation between SHP-1 protein expression and tyrosine phosphorylated state of JAK3, the state of phosphorylation of JAK3 was studied in the T cell line HUT-78, and found to be highly phosphorylated. These results suggest that SHP-1 might be involved in maintaining the IL-2R/JAK3 signaling pathway under control and point towards a role of SHP-1 in the pathogenesis of the disease.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Matthew RJ, Bowne DB, Flores E, Thomas ML . Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences Mol Cel Biol 1992 12: 2396–2405
Pani G, Fischer K-D, Mlinaric-Rascan I, Siminovitch KA . Signaling capacity of the T cell antigen receptor is negatively regulated by the PTP1C tyrosine phosphatase J Exp Med 1996 184: 839–852
Johnson KG, LeRoy FG, Borysiewicz LK, Matthews RJ . T cell receptor signaling thresholds regulating T cell development and activation are dependent upon SHP-1 J Immunol 1999 162: 3802–3813
Pani G, Kozlowski M, Cambier JC, Mills GB, Siminovitch KA . Identification of the tyrosine phosphatase PTP1C as the B cell antigen receptor-associated protein involved in the regulation of the B cell signaling J Exp Med 1995 181: 2077–2084
Law C-L, Sidorenko SP, Chandran KA, Zhao Z, Shen S-H, Fischer E, Clark EA . CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-γ1 upon B cell activation J Exp Med 1996 183: 547–560
Olcese L, Lang P, Vély F, Cambiaggi A, Marguet D, Bléry M, Hippen KL, Biassoni R, Moretta A, Moretta L, Cambier JC, Vivier E . Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases J Immunol 1996 156: 4531–4534
Klingmüller U, Lorenz U, Cantley LC, Neel BG, Lodish HF . Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals Cell 1995 80: 729–739
Yi T, Ahang J, Miurs O, Ihle JN . Hematopoietic cell phosphatase associates with erythropoietin (Epo) receptor after Epo-induced tyrosine-phosphorylation: identification of potential binding sites Blood 1995 85: 87–95
Yetter A, Uddin S, Krolewski JJ, Jiao H, Yi T, Platanias LC . Association of the interferon-dependent tyrosine-kinase Tyk-2 with the hematopoietic cell phosphatase J Biol Chem 1995 270: 18179–18182
Ram PA, Waxman DJ . Interaction of the growth hormone-activated STATs with SH2-containing phosphotyrosine phosphatase SHP-1 and nuclear JAK2 tyrosine kinase J Biol Chem 1997 272: 17694–17702
Migone TS, Cacalano NA, Taylor N, Yi T, Waldman TA, Johnson JA . Recruitment of SH2-containing protein tyrosine phosphatase SHP-1 to the interleukin 2 receptor; loss of SHP-1 expression in human T-lymphotropic virus type I-transformed T cells Proc Natl Acad Sci USA 1998 95: 3845–3850
Haquet SJ, Harbor P, Tabrizi M, Yi T, Williams BRG . Protein-tyrosine phosphatase SHP-1 is a negative regulator of IL-4 and IL-13-dependent signal transduction J Biol Chem 1998 273: 33893–33896
Lorenz U, Ravichandran KS, Burakoff SJ, Neel BG . Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness Proc Natl Acad Sci USA 1996 93: 9424–9629
Plas DR, Johnson R, Pingel JT, Mattews RJ, Dalton M, Roy G, Chan AC, Thomas ML . Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling Science 1996 272: 1173–1176
Witthuhn BA, Silvennonien O, Miura O, Lai KS, Cwick C, Llu ET, Ihie JN . Involvement of the Jak-3 Janus Kinase in signaling by interleukins 2 and 4 in lymphoid and myeloid cells Nature 1994 370: 153–157
Beadling C, Guschin D, Witthuhn BA, Ziemiecki A, Ihle JN, Kerr IM, Cantrell DA . Activation of JAK kinases and STAT proteins by interleukin-2 and interferon-α, but not the T cell antigen receptor, in human T lymphocytes EMBO J 1994 13: 5605–5615
Shultz LD, Schweitzer PA, Rajan TV, Yi T, Ihle JN, Matthews RJ, Thomas ML, Beier DR . Mutations at the murine motheaten locus are within the hematopoietic cell protein–tyrosine phosphatase (Hcph) gene Cell 1993 73: 1445–1454
Delibrias CC, Floettmann JE, Rowe M, Fearon DT . Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes J Exp Med 1997 186: 1575–1583
Wickrema A, Chen F, Namin F, Yi T, Ahmad S, Uddin S, Chen Y-H, Feldman L, Stock L, Hoffman R, Platanias LC . Defective expression of the SHP-1 phosphatase in polycythemia vera Exp Hematol 1999 27: 1124–1132
Zhang Qia, Raghunath PN, Vonderheid E, Odum N, Wasik MA . Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter Am J Pathol 2000 157: 1137–1146
Zhang Q, Nowak I, Vonderheid EC, Rook AH, Kadin ME, Nowell PC, Shaw LM, Wasik MA . Activation of Jak/STAT proteins involved in signal transduction pathway mediated by receptor for interleukin 2 in malignant T lymphocytes derived from cutaneous anaplastic large T-cell lymphoma and Sezary syndrome Proc Natl Acad Sci USA 1996 93: 9148–9153
Migone TS, Lin JX, Cereseto A, Mulloy JC, O‘Shea JJ, Franchini G, Leonard WJ . Constitutively activated Jak STAT pathway in T cells transformed with HTLV-I Science 1995 269: 79–81
Gaznar AF, Carney DN, Bunn PA, Russell EK, Jaffe ES, Schechter GP, Guccion JG . Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas Blood 1980 55: 409–417
Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, Diaz-Perez JL, Geerts ML, Goos M, Knobler R, Ralfkiaer E, Santucci M, Smith N, Wechsler J, van Vloten WA, Meijer CJ . EORTC classification for primary cutaneous lymphomas: a proposal from Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer Blood 1997 90: 354–371
Willemze R, Meijer CJ . EORTC classification for primary cutaneous lymphomas: the best guide to good clinical management. European Organization for Research and Treatment of Cancer Am J Dermatopathol 1999 21: 265–273
Döbbeling U, Dummer R, Laine E, Potoczna N, Qin J-Z, Burg G . Interleukin-15 is an autocrine paracrine viability factor for cutaneous T-cell lymphoma cells Blood 1998 92: 252–258
Beghini A, Ripamonti CD, Peterlongo P, Roversi G, Cairoli R, Morra E, Larizza L . RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia Hum Mol Genet 2000 9: 2297–2304
Zhang Q, Lee B, Korecka M, Li G, Weyland C, Eck S, Gessain A, Arima N, Lessin SR, Shaw LM, Luger S, Kamoun M, Wasik MA . Differences in phosphorylation of the IL-2R associated JAK/STAT proteins between HTLV-I (+), IL-2-independent and IL-2-dependent cell lines and uncultured leukemic cells from patients with adult T-cell lymphoma/leukemia Leukemia Res 1999 23: 373–384
Brender C, Nielsen M, Kaltoft K, Mikkelsen G, Zhang Q, Wasik M, Billestrup N, Odum N . STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma Blood 2001 97: 1056–1062
Acknowledgements
This work was supported by the FIS grants 00/0196 and 00/410.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
León, F., Cespón, C., Franco, A. et al. SHP-1 expression in peripheral T cells from patients with Sezary syndrome and in the T cell line HUT-78: implications in JAK3-mediated signaling. Leukemia 16, 1470–1477 (2002). https://doi.org/10.1038/sj.leu.2402546
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2402546
Keywords
This article is cited by
-
Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma
Molecular Medicine (2022)
-
Constitutive activation of STAT3 in Sézary syndrome is independent of SHP-1
Leukemia (2012)
-
SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients
Laboratory Investigation (2008)
-
Jak3 contributes to the activation of ALK and Stat3 in ALK+ anaplastic large cell lymphoma
Laboratory Investigation (2006)