DARPP-32 (dopamine and adenosine 3', 5'-cyclic monophosphate cAMP-regulated phosphoprotein, 32 kDa) is a striatal-enriched protein that mediates signaling by dopamine and other first messengers in the medium spiny neurons. The transcriptional mechanisms that regulate striatal DARPP-32 expression remain enigmatic and are a subject of much interest in the efforts to induce a striatal phenotype in...

We recently reported the use of a gene-trapping approach to isolate cell clones in which a reporter gene had integrated into genes modulated by T-cell activation. We have now tested a panel of clones from that report and identified the one that responds to a variety of G-protein coupled receptors (GPCR). The beta-lactamase tagged EGR-3 Jurkat cell was used to dissect specific GPCR signaling in ...

Background and Purpose—Unstable atherosclerotic plaques are characterized by increased macrophages and reduced smooth muscle cells (SMCs) and collagen content. Endoglin, an accessory transforming growth factor(TGF ) receptor, is a modulator of TGF signaling recently found to be expressed on SMCs in atherosclerotic plaques. Its function in plaque SMCs and plaque development is unknown. Early gro...

Tumor-bone marrow microenvironment interactions in multiple myeloma (MM) are documented to play crucial roles in plasma-cell growth/survival. In vitro coculture of MM cells with osteoclasts supported cell survival and significantly down-regulated JUN expression. JUN expression in myeloma cells from late-stage and high-risk MM was significantly lower than in plasma cells from healthy donors, mon...

Egr-1 is an immediate early gene that couples short-term changes in the extracellular milieu to long-term changes in gene expression. Under in vitro conditions, the Egr-1 gene is expressed in many cell types and is induced by a wide variety of extracellular signals. The mechanisms by which the Egr-1 gene is regulated in vivo remain poorly understood. In this study, we have generated transgenic ...

Using a variety of differentiation-inducible myeloid cell lines, we previously showed that the zinc-finger transcription factor early growth response gene 1 (Egr-1) is a positive modulator of macrophage differentiation and negatively regulates granulocytic differentiation. In this study, high-efficiency retroviral transduction was used to ectopically express Egr-1 in myeloid-enriched or stem ce...

5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in chemotherapy against various solid tumors. 5-FU dose-dependently increased the expression levels of intrinsic antiangiogenic factor thrombospondin-1 (TSP-1) in human colon carcinoma KM12C cells and human breast cancer MCF7 cells. We investigated the molecular basis for the induction of TSP-1 by 5-FU in KM12C cells. Promo...

Early growth response (Egr) proteins comprise a family of transcriptional regulators (Egr1-4) that modulate gene expression involved in the growth and differentiation of many cell types. In particular, Egr1 is widely believed to have an essential role in regulating monocyte/macrophage differentiation. However, Egr1-deficient mice have normal numbers of functional macrophages, an observation tha...

We recently established that the EGF-R (epidermal growth factor receptor) (EGF-R) is an essential regulator of the reactive expansion of SVZ (subventricular zone) NPs (neural precursors) that occurs during recovery from hypoxic-ischemic brain injury. The purpose of the current studies was to identify the conditions and the transcription factor (s) responsible for inducing the EGF-R. Here, we sh...

BACKGROUND AND PURPOSE Unstable atherosclerotic plaques are characterized by increased macrophages and reduced smooth muscle cells (SMCs) and collagen content. Endoglin, an accessory transforming growth factor-beta (TGFbeta) receptor, is a modulator of TGFbeta signaling recently found to be expressed on SMCs in atherosclerotic plaques. Its function in plaque SMCs and plaque development is unkno...