TY - JOUR
T1 - T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6
AU - Lu, Xiaoqing
AU - Chen, Jun
AU - Sasmono, Tedjo
AU - Hsi, Eric D
AU - Sarosiek, Kristopher A
AU - Tiganis, Tony
AU - Lossos, Izidore S
PY - 2007
Y1 - 2007
N2 - Diffuse large B-cell lymphomas (DLBCL) 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 IL-4 responsiveness and STAT6 signaling in these DLBCL subtypes. Increased nuclear dephosphorylation of 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 DLBCL may contribute to the different biological characteristics of these tumors.
AB - Diffuse large B-cell lymphomas (DLBCL) 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 IL-4 responsiveness and STAT6 signaling in these DLBCL subtypes. Increased nuclear dephosphorylation of 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 DLBCL may contribute to the different biological characteristics of these tumors.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17210636
M3 - Article
VL - 27
SP - 2166
EP - 2179
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 6
ER -