Negative regulatory role of annexin-A1 in 14-3-3eta-mediated glucocorticoid receptor transcriptional activation.

Annexin-A1 (ANX-1) is involved in glucocorticoid receptor (GR)-mediated signal transduction. However, the molecular mechanism by which ANX-1 plays a role in GR signaling is not fully understood. Recently, we reported that 14-3-3eta inhibits degradation of GR, resulting in an increase in GR transcriptional activity.

Human CC chemokine CCL23, a ligand for CCR1, induces endothelial cell migration and promotes angiogenesis.

A number of chemokines induce angiogenesis and endothelial cells express several chemokine receptors. To date, only a limited number of CC chemokines for CCR1 have been reported to induce angiogenic responses. We investigated the ability of CCL23 (also known as MPIF-1, MIP-3, or CKbeta8) to promote angiogenesis, which induces chemotaxis of immune cells through CCR1.

Role of 14-3-3 eta as a positive regulator of the glucocorticoid receptor transcriptional activation.

The glucocorticoid receptor (GR), a member of the nuclear receptor superfamily, mediates the effects of glucocorticoids. It is known that 14-3-3 family proteins interact with GR and regulate its transcriptional activity. They also bind to several molecules and influence many cellular events by altering their subcellular localization and/or acting as a chaperone.

PLP2/A4 interacts with CCR1 and stimulates migration of CCR1-expressing HOS cells.

Multiple CC chemokines bind to CCR1, which plays important roles in immune and inflammatory responses. To search for proteins involved in the CCR1 signaling pathway, we screened a yeast two-hybrid library using the cytoplasmic tail of CCR1 as the bait. One of the positive clones contained an open reading frame of 456bp, of which the nucleotide sequence was identical to that of proteolipid protein 2 (PLP2), also known as protein A4.

Proteomic analysis of differential protein expression in neuropathic pain and electroacupuncture treatment models.

Acupuncture has long been used for pain relief. Although recent studies have shown that acupuncture can reduce neuropathic pain, the mechanism of this effect is not clear and little information is available regarding proteins that are involved in the development of neuropathic pain and the effects of acupuncture. We have developed an animal model for neuropathic pain using young adult male Sprague-Dawley rats.

Differential effects of 9-cis retinoic acid on expression of CC chemokine receptors in human monocytes.

9-cis Retinoic acid (9-CRA) is a lipophilic molecule that binds to the retinoid X receptor (RXR). Although retinoic acid (RA) has been known to regulate neutrophil differentiation, a specific role for 9-CRA in chemokine-mediated cellular processes remains obscure. We investigated the effects of 9-CRA on expression of CC chemokine receptors (CCRs) in human monocytic THP-1 cells and peripheral blood monocytes.

Angiogenic activity of human CC chemokine CCL15 in vitro and in vivo.

CCL15 is a novel human CC chemokine and exerts its biological activities on immune cells through CCR1 and CCR3. Because a number of chemokines induce angiogenesis and endothelial cells express CCR1 and CCR3, we investigated the angiogenic activity of CCL15. Both CCL15(1-92) and N-terminal truncated CCL15(25-92) stimulate the chemotactic endothelial cell migration and differentiation, but CCL15(25-92) is at least 100-fold more potent than CCL15(1-92).

Transcriptional and post-transcriptional regulation of the PKC delta gene by etoposide in L1210 murine leukemia cells: implication of PKC delta autoregulation.

Protein kinase C delta (PKC delta) plays an important role in the regulation of apoptosis in response to diverse anticancer agents. PKC delta is cleaved irreversibly to a catalytically active fragment in response to apoptotic stimuli; however, little information is available about the regulation of PKC delta gene expression. In this study, we found that the amount of steady-state PKC delta mRNA and protein was increased by etoposide in mouse L1210 leukemia cells.

Human LZIP binds to CCR1 and differentially affects the chemotactic activities of CCR1-dependent chemokines.

Signaling molecules that bind to chemokine receptors should play key roles in regulation of cell migration induced by chemokines. To characterize the CCR1-mediated cellular signal transduction mechanism, we used the yeast two-hybrid system to identify a cellular ligand for CCR1. LZIP, which has been known as a transcription factor in various cell types, was identified as a CCR1 binding protein.

Transgenic mouse model for breast cancer: induction of breast cancer in novel oncogene HCCR-2 transgenic mice.

Transgenic mice containing novel oncogene HCCR-2 were generated to analyse the phenotype and to characterize the role of HCCR-2 in cellular events. Mice transgenic for HCCR-2 developed breast cancers and metastasis. The level of p53 in HCCR-2 transgenic mice was elevated in most tissues including breast, brain, heart, lung, liver, stomach, kidney, spleen, and lymph node.

Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKC delta/Ras cascades in HOS cells.

Recently cloned leukotactin-1 (Lkn-1) that belongs to CC chemokine family has not been characterized. To understand the intracellular events following Lkn-1 binding to CCR1, we investigated the activities of signaling molecules in response to Lkn-1 in human osteogenic sarcoma cells expressing CCR1. Lkn-1-stimulated cells showed elevated phosphorylation of extracellular signal-related kinases (ERK1/2) with a distinct time course.

Membrane rafts play a crucial role in receptor activator of nuclear factor kappaB signaling and osteoclast function.

Membrane lipid rafts play a key role in immune cell activation by recruiting and excluding specific signaling components of immune cell surface receptors upon the receptor engagement. Despite this, the role of these microdomains in the regulation of osteoclasts as controlled by receptor activator of nuclear factor kappaB (RANK) has yet to be established. In this study, we demonstrate that the raft microdomain expression plays an essential role in osteoclast function and differentiation.

Lignans with inhibitory activity against NFAT transcription from Schisandra chinensis.

Seven lignans from Schisandra chinensis were investigated for their inhibitory activity on NFAT transcription. Both gomisin N (IC 50 : 1.33 +/- 0.

Dynamic inhibition of nuclear receptor activation by corepressor binding.

Nuclear receptors adopt dramatically different conformations in the presence or absence of ligand, and such liganded (holo) and unliganded (apo) receptors are specifically recognized by transcriptional coactivators and corepressors, respectively. These two states likely exist in dynamic equilibrium, contrary to the conventional model of static off and on conformations. First, corepressor SMRT [for silencing mediator of thyroid hormone receptor (TR) and retinoic acid receptor (RAR)] inhibits the interaction of coactivator steroid receptor coactivator-1 with liganded TR/RAR.

Human secreted frizzled-related protein is down-regulated and induces apoptosis in human cervical cancer.

To identify genes involved in cervical carcinogenesis, the mRNA differential display method was used. A 220-bp cDNA fragment called CA11 was present in normal cervical tissue but not in primary cervical cancer tissue or cervical cancer cell lines. CA11 exhibited 98% homology with the recorded human secreted frizzled-related protein (hsFRP) sequence.

Negative regulatory role of overexpression of PLC gamma 1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts.

The early growth response 1 (Egr-1) gene product is a transcription factor that functions as an oikis factor. Loss of Egr-1 expression is closely associated with tumor formation. Phospholipase Cgamma1 (PLCgamma1) is overexpressed in some tumors, and its overexpression causes anchorage-independent growth.

cDNA microarray analysis of the differential gene expression in the neuropathic pain and electroacupuncture treatment models.

Partial nerve injury is the main cause of neuropathic pain disorders in humans. Acupuncture has long been used to relieve pain. It is known to relieve pain by controlling the activities of the autonomic nervous system.

Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells.

Leukotactin-1 (Lkn-1)/CCL15 is a recently cloned CC-chemokine that binds to the CCR1 and CCR3. Although Lkn-1 has been known to function as a chemoattractant for neutrophils, monocytes and lymphocytes, its cellular mechanism remains unclear. To understand the mechanism of Lkn-1-induced chemotaxis signaling, we examined the chemotactic activities of human osteogenic sarcoma cells expressing CCR1 in response to Lkn-1 using inhibitors of signaling molecules.

Truncation of NH2-terminal amino acid residues increases agonistic potency of leukotactin-1 on CC chemokine receptors 1 and 3.

Leukotactin-1 (Lkn-1) is a human CC chemokine that binds to both CC chemokine receptor 1 (CCR1) and CCR3. Structurally, Lkn-1 is distinct from other human CC chemokines in that it has long amino acid residues preceding the first cysteine at the NH(2) terminus, and contains two extra cysteines. NH(2)-terminal amino acids of Lkn-1 were deleted serially, and the effects of each deletion were investigated.

Molecular cloning and characterization of CAPER, a novel coactivator of activating protein-1 and estrogen receptors.

Transcriptional coactivators either bridge transcription factors and the components of the basal transcription apparatus and/or remodel the chromatin structures. We isolated a novel nuclear protein based on its interaction with the recently described general coactivator activating signal cointegrator-2 (ASC-2). This protein CAPER (for coactivator of activating protein-1 (AP-1) and estrogen receptors (ERs)) selectively bound, among the many transcription factors we tested, the AP-1 component c-Jun and the estradiol-bound ligand binding domains of ERalpha and ERbeta.