Biomedical subjects

R Tedjo Sasmono

Publications and source records attributed to R Tedjo Sasmono.

3 recordsLinked to original sources

PubMed2007

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

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.

Catalytic Domain↗

PubMed2002

A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse.

The c-fms gene encodes the receptor for macrophage colony-stimulating factor (CSF-1). The gene is expressed selectively in the macrophage and trophoblast cell lineages. Previous studies have indicated that sequences in intron 2 control transcript elongation in tissue-specific and regulated expression of c-fms. In humans, an alternative promoter was implicated in expression of the gene in trophoblasts. We show that in mice, c-fms transcripts in trophoblasts initiate from multiple points within the 2-kilobase (kb) region flanking the first coding exon. A reporter gene construct containing 3.5 kb of 5' flanking sequence and the downstream intron 2 directed expression of enhanced green fluorescent protein (EGFP) to both trophoblasts and macrophages. EGFP was detected in trophoblasts from the earliest stage of implantation examined at embryonic day 7.5. During embryonic development, EGFP highlighted the large numbers of c-fms-positive macrophages, including those that originate from the yolk sac. In adult mice, EGFP location was consistent with known F4/80-positive macrophage populations, including Langerhans cells of the skin, and permitted convenient sorting of isolated tissue macrophages from disaggregated tissue. Expression of EGFP in transgenic mice was dependent on intron 2 as no lines with detectable EGFP expression were obtained where either all of intron 2 or a conserved enhancer element FIRE (the Fms intronic regulatory element) was removed. We have therefore defined the elements required to generate myeloid- and trophoblast-specific transgenes as well as a model system for the study of mononuclear phagocyte development and function.

Animals↗

PubMed2002

The mononuclear phagocyte system revisited.

The mononuclear phagocyte system (MPS) was defined as a family of cells comprising bone marrow progenitors, blood monocytes, and tissue macrophages. In this review, we briefly consider markers for cells of this lineage in the mouse, especially the F4/80 surface antigen and the receptor for macrophage colony-stimulating factor. The concept of the MPS is challenged by evidence that there is a separate embryonic phagocyte lineage, the blurring of the boundaries between macrophages and other cells types arising from phenotypic plasticity and transdifferentiation, and evidence of local renewal of tissue macrophage populations as opposed to monocyte recruitment. Nevertheless, there is a unity to cells of the MPS suggested by their location, morphology, and shared markers. We discuss the origins of macrophage heterogeneity and argue that macrophages and antigen-representing dendritic cells are closely related and part of the MPS.

Animals↗