Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate.

Plk1 (Polo-like kinase 1), an evolutionarily conserved serine/threonine kinase, is crucially involved in multiple events during the M phase. Here we have identified a consensus phosphorylation sequence for Plk1, by testing the ability of systematically mutated peptides derived from human Cdc25C to serve as a substrate for Plk1. The obtained results show that a hydrophobic amino acid at position +1 carboxyl-terminal of phosphorylated Ser/Thr and an acidic amino acid at position -2 are important for optimal phosphorylation by Plk1.

AKRL1 and AKRL2 activate the JNK pathway.

Background: c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is activated by specific cytokines and various environmental stresses. MKK4 and MKK7 are shown to be direct activators of JNK. Although several upstream components of the JNK pathway, including members of the MAPKKK family have been described, the components lying between the receptors or sensors and JNK have not been fully characterized.

Molecular recognitions in the MAP kinase cascades.

The mitogen-activated protein kinase (MAPK) cascades play a pivotal role in many aspects of cellular functions, and are evolutionarily conserved from yeast to mammals. In mammals, there are four subfamily members in the MAPKs. Each MAPK has its own activators, substrates and inactivators.

Regulation of c-Fos and Fra-1 by the MEK5-ERK5 pathway.

Background: ERK5 is the newest subfamily member of the mitogen-activated protein kinase (MAPK) family, and is activated by various extracellular signals including growth factors. MEK5 is a specific activator of ERK5. c-Fos and Fra-1, well-known immediate early gene products, are members of the AP-1 family.

Identification of a DAF-16 transcriptional target gene, scl-1, that regulates longevity and stress resistance in Caenorhabditis elegans.

In Caenorhabditis elegans, an insulin-like signaling pathway, which includes the daf-2 and age-1 genes, controls longevity and stress resistance. Downregulation of this pathway activates the forkhead transcription factor DAF-16, whose transcriptional targets are suggested to play an essential role in controlling the phenotypes governed by this pathway. We have surveyed the genes that have the DAF-16 consensus binding element (DBE) within putative regulatory regions.

Factors contributing to tooth retention among elderly women.

The purpose of this study is to identify factors contributing to tooth retention. A questionnaire was prepared which includes 22 main items concerning oral health care. The questionnaire was answered by 144 females in their 80's at 4 Health and Welfare Centers for the Aged in the City of Naha in July 1995 through interview format.

Essential role of the transcription factor Ets-2 in Xenopus early development.

The fibroblast growth factor (FGF)/MAPK pathway plays an important role in early Xenopus developmental processes, including mesoderm patterning. The activation of the MAPK pathway leads to induction of Xenopus Brachyury (Xbra), which regulates the transcription of downstream mesoderm-specific genes in mesoderm patterning. However, the link between the FGF/MAPK pathway and the induction of Xbra has not been fully understood.

Renal function tests on diabetes-induced and non-induced APA hamsters.

Although it has been said that Syrian hamsters of the APA strain (APA hamsters) spontaneously develop glomerulosclerosis with age, more prominent and severe glomerulosclerosis with proteinuria as well as arteriosclerosis is induced in diabetic APA hamsters. In this study, in order to supply new information on APA hamsters, tests on renal function and histology were done on non-diabetic and streptozotocin (SZ)-induced diabetic APA hamsters (APA-N and APA-D, respectively), and the data were compared with those of normal Syrian (golden) hamsters (GOL). At 4, 8, 12, 20, and 32 weeks of age, the markers indicating renal function, serum urea nitrogen and creatinine levels and the urinary total protein level were measured and thereafter histological studies were done.

Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway.

Sprouty (Spry) inhibits signalling by receptor tyrosine kinases; however, the molecular mechanism underlying this function has not been defined. Here we show that after stimulation by growth factors Spry1 and Spry2 translocate to the plasma membrane and become phosphorylated on a conserved tyrosine. Next, they bind to the adaptor protein Grb2 and inhibit the recruitment of the Grb2-Sos complex either to the fibroblast growth factor receptor (FGFR) docking adaptor protein FRS2 or to Shp2.

Nuclear translocation of plk1 mediated by its bipartite nuclear localization signal.

Polo-like kinase 1 (Plk1), a mammalian ortholog of Drosophila Polo, is a serine-threonine protein kinase implicated in the regulation of multiple aspects of mitosis. The protein level, activity, and localization of Plk1 change during the cell cycle, and its proper subcellular localization is thought to be crucial for its function. Although localization of Plk1 to the centrosome has been established, nuclear localization or nucleocytoplasmic translocation of Plk1 has not been fully addressed.

Catheter dysfunction and thrombosis of double-lumen hemodialysis catheters placed in the femoral vein.

Objective: Intraluminal thrombosis of the catheter was thought to be a major cause of catheter dysfunction. We evaluated if thrombi appear in the luminal side or outside of the catheters placed in the femoral vein in 21 hemodialysis patients.

Methods: 23 double-lumen catheter (25 cm long and 4 mm diameter polyurethane) strippings were consecutively performed.

Docking interactions in the mitogen-activated protein kinase cascades.

Regulation of cellular functions and responses utilizes a number of the signal transduction pathways. Each pathway should transduce signals with high efficiency and fidelity to avoid unnecessary crosstalks. The mitogen-activated protein kinase (MAPK) cascades regulate a wide variety of cellular functions, including cell proliferation, differentiation, and stress responses.

Identification of the Anti-proliferative protein Tob as a MAPK substrate.

Mitogen-activated protein kinases (MAPKs) regulate a wide variety of cellular functions by phosphorylating their specific substrates. Here we have identified Tob as a novel substrate of MAPK. Tob, a member of the Tob and B-cell translocation gene anti-proliferative protein family, is shown to negatively regulate the proliferation of osteoblasts and T cells.

Characterization of TH1/TH2 profile in uremic patients.

End-stage renal failure (ESRD) induces a clinical state of immunodeficiency with a higher incidence of infections and a higher mortality due to infectious complications compared with the normal population. Using a newly developed immunofluorescent staining of intracellular cytokines for flow cytometric analysis, we studied Th subsets in 22 healthy control subjects, 28 patients with compensated chronic renal failure (CRF), 25 patients on hemodialysis (HD), and 24 patients on continuous ambulatory peritoneal dialysis (CAPD). Our results demonstrate that the percentage of both interferon-gamma-positive cells and interleukin-4-positive cells increased in compensated CRF patients compared with those in healthy subjects.

Modular structure of a docking surface on MAPK phosphatases.

Mitogen-activated protein kinases (MAPKs) must be precisely inactivated to achieve proper functions in the cells. Ten members of dual specificity phosphatases specifically acting on MAPKs, termed MAPK phosphatases (MKPs), have been reported. Each member has its own substrate specificity that should be tightly regulated.

The GTPase Ran regulates chromosome positioning and nuclear envelope assembly in vivo.

The GTPase Ran is known to regulate transport of proteins across the nuclear envelope. Recently, Ran has been shown to promote microtubule polymerization and spindle assembly around chromatin in Xenopus mitotic extracts and to stimulate nuclear envelope assembly in Xenopus or HeLa cell extracts. However, these in vitro findings have not been tested in living cells and do not necessarily describe the generalized model of Ran functions.

Plk1 promotes nuclear translocation of human Cdc25C during prophase.

The nuclear accumulation of active M-phase promoting factor (MPF) during prophase is thought to be essential for coordinating M-phase events in vertebrate cells. The protein phosphatase Cdc25C, an activator of MPF, enters the nucleus to keep MPF active in the nucleus during prophase. However, the molecular mechanisms that control nuclear translocation of Cdc25C during prophase are unknown.

Functional and histochemical analysis on pancreatic islets of APA hamsters with SZ-induced hyperglycemia and hyperlipidemia.

To clarify how Syrian hamsters of the APA strain (APA hamsters) keep a diabetic condition for a long period, the functional and histochemical changes in the pancreatic islets of diabetic APA hamsters were examined. By glucose tolerance test, no glucose-induced insulin secretion was seen in the diabetic APA hamsters. By immunohistochemistry, it was revealed that at 24 hr after SZ-injection, the number of islets had decreased and that remnant islets had become markedly smaller.

Expression of lipoprotein receptors in the aortic walls of diabetic APA hamsters.

Syrian hamsters of the APA strain (APA hamsters) have recently been demonstrated to develop atheromatous lesions in the aortic arches under the diabetic condition induced by a single injection of streptozotocin (SZ). Various lipoprotein receptors are reported to play important roles in atherogenesis mainly in vitro, while there are few reports on the relative expressions of these receptors in vivo. In this study, we therefore examined messenger RNA (mRNA) expressions of several lipoprotein receptors on the aortic arches of diabetic APA hamsters at 6, 14 and 26 weeks after the injection (WAI) of SZ.

Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells.

Recent studies have shown that casein kinase I epsilon (CKIepsilon) is an essential regulator of the mammalian circadian clock. However, the detailed mechanisms by which CKIepsilon regulates each component of the circadian negative-feedback loop have not been fully defined. We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta.

JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates.

Recent genetic studies in Drosophila identified a novel non-canonical Wnt pathway, the planar cell polarity (PCP) pathway, that signals via JNK to control epithelial cell polarity in Drosophila. Most recently, a pathway regulating convergent extension movements during gastrulation in vertebrate embryos has been shown to be a vertebrate equivalent of the PCP pathway. However, it is not known whether the JNK pathway functions in this non-canonical Wnt pathway to regulate convergent extension movements in vertebrates.

Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway.

Leucine zipper-bearing kinase (LZK) is a novel member of the mixed lineage kinase (MLK) protein family, the cDNA of which was first cloned from a human brain cDNA library [Sakuma, H., Ikeda, A., Oka, S.

Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5.

Background: Runx2, formerly called PEBP2alphaA or Cbfa1, is a transcription factor whose deletion causes a complete lack of ossification. It directly regulates the expression of osteoblast-specific genes through the osteoblast-specific cis-acting element found in the promoter region of these genes.

Results: In this study, we have found conditions in which induction of the expression of Runx2 is not accompanied by expression of an osteoblast-specific gene, osteocalcin in C2C12 cells.