T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6

Xiaoqing Lu, Jun Chen, R. Tedjo Sasmono, Eric D. Hsi, Kristopher A. Sarosiek, Tony Tiganis, Izidore Lossos

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Diffuse large B-cell lymphomas (DLBCLs) consist of clinically distinct subtypes: germinal center B-cell (GCB)-like and activated-B-cell (ABC)-like tumors, characterized by long and short survival, respectively. We reported distinct interleukin 4 (IL-4) responsiveness and STAT6 signaling in these DLBCL subtypes. Increased nuclear dephosphorylation of phospho-STAT6 (pSTAT6) was observed in ABC-like tumors, which exhibited a different expression profile of protein tyrosine phosphatases (PTPs). Among the differentially expressed PTPs, only T-cell PTP (TCPTP) localizes to the nucleus. Herein, we report that the elevated expression of TCPTP in ABC- versus GCB-like DLBCL tumors is not due to the distinct ontogeny of these neoplasms but rather may be an acquired feature of the tumors. Moreover, we report that STAT6 may serve as a physiological nuclear substrate for TCPTP. We demonstrate interactions between endogenous TCPTP and STAT6 and delineate the domains responsible for the interaction. Overexpression of TCPTP ameliorates IL-4-induced STAT6 phosphorylation and associated gene transcription, whereas knockdown of endogenous TCPTP results in increased IL-4-induced STAT6 signaling. Moreover, we report that TCPTP protein levels may be increased in response to IL-4 and that TCPTP may serve in a negative feedback loop for the suppression of IL-4-induced signaling. Taken together, these results identify TCPTP as a physiological regulator of STAT6 phosphorylation and suggest that specific increases in TCPTP expression in ABC-like DLBCLs may contribute to the different biological characteristics of these tumors.

Original languageEnglish
Pages (from-to)2166-2179
Number of pages14
JournalMolecular and Cellular Biology
Volume27
Issue number6
DOIs
StatePublished - Mar 1 2007

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Non-Receptor Type 2 Protein Tyrosine Phosphatase
Lymphoma, Large B-Cell, Diffuse
Phosphoric Monoester Hydrolases
B-Lymphocytes
T-Lymphocytes
Interleukin-4
Neoplasms
Protein Tyrosine Phosphatases
Germinal Center
Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6. / Lu, Xiaoqing; Chen, Jun; Sasmono, R. Tedjo; Hsi, Eric D.; Sarosiek, Kristopher A.; Tiganis, Tony; Lossos, Izidore.

In: Molecular and Cellular Biology, Vol. 27, No. 6, 01.03.2007, p. 2166-2179.

Research output: Contribution to journalArticle

Lu, Xiaoqing ; Chen, Jun ; Sasmono, R. Tedjo ; Hsi, Eric D. ; Sarosiek, Kristopher A. ; Tiganis, Tony ; Lossos, Izidore. / T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 6. pp. 2166-2179.
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AU - Hsi, Eric D.

AU - Sarosiek, Kristopher A.

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AU - Lossos, Izidore

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