Phytohormones participate in an S6 kinase signal transduction pathway in Arabidopsis

Addition of fresh medium to stationary cells of Arabidopsis suspension culture induces increased phosphorylation of the S6 ribosomal protein and activation of its cognate kinase, AtS6k. Analysis of the activation response revealed that medium constituents required for S6 kinase activation were the phytohormones 1-naphthylacetic acid (auxin) and kinetin. Pretreatment of cells with anti-auxin or PI3-kinase drugs inhibited this response. Consistent with these findings, LY294002, a PI3-kinase inhibitor, efficiently suppressed phytohormone-induced S6 phosphorylation and translational up-regulation of ribosomal protein S6 and S18A mRNAs without affecting global translation. These data indicate that (1) activation of AtS6k is regulated by phytohormones, at least in part, via a lipid kinase-dependent pathway, that (2) the translational regulation of ribosomal proteins appears to be conserved throughout the plant and animal kingdom, and that (3) these events are hallmarks of a growth-related signal transduction pathway novel in plants.     

Nephrin 信号转导机制研究进展

Nephrin作为肾小球足细胞膜上的跨膜蛋白,是足细胞裂隙膜重要的结构分子。近来发现,nephrin分子细胞内段的酪氨酸残基在被酪氨酸激酶fyn（属Src激酶家族成员）磷酸化后,能激活下游信号分子,形成足细胞内特有的信号转导通路,如nephrin—podocin—MAPK—AP-1、nephrin—CD2AP-P13K-Akt／PKB、nephrin-Nck—Rac／CDC42等。这些信号通路参与了足细胞胚胎发生、细胞生存与细胞骨架重组等许多重要生理病理过程的调节。同样,nephrin蛋白及mRNA的表达也受许多因素的调节。研究nephrin及其信号转导机制对了解并防治肾小球硬化有重要意义。     

Chaperones in cell cycle regulation and mitogenic signal transduction: a review

Chaperones/heat shock proteins (HSPs) of the HSP90 and HSP70 families show elevated levels in proliferating mammalian cells and a cell cycle-dependent expression. They transiently associate with key molecules of the cell cycle control system such as Cdk4, Wee-1, pRb, p53, p27/Kip1 and are involved in the nuclear localization of regulatory proteins. They also associate with viral oncoproteins such as SV40 super T, large T and small t antigen, polyoma large and middle S antigen and EpsteinBarr virus nuclear antigen. This association is based on a J-domain in the viral proteins and may assist their targeting to the pRb/E2F complex. Small HSPs and their state of phosphorylation and oligomerization also seem to be involved in proliferation and differentiation. Chaperones/HSPs thus play important roles within cell cycle processes. Their exact functioning, however, is still a matter of discussion. HSP90 in particular, but also HSP70 and other chaperones associate with proteins of the mitogen-activated signal cascade, particularly with the Src kinase, with tyrosine receptor kinases, with Raf and the MAP-kinase activating kinase (MEK). This apparently serves the folding and translocation of these proteins, but possibly also the formation of large immobilized complexes of signal transducing molecules (scaffolding function).     

Casein kinase II in signal transduction and cell cycle regulation

Molecular and Cellular Biochemistry - Casein kinase II is a protein serine/threonine kinase that is ubiquitously distributed in eukaryotes. Molecular cloning studies and protein sequence analysis...     

IgE介导的肥大细胞脱颗粒信号转导途径的研究进展

肥大细胞(mast cell,MC)是过敏性疾病的关键细胞之一.机体的过敏反应很大程度依赖于肥大细胞膜上的特异性受体FcεRI.肥大细胞膜上交联的FcεRI引发了下游的一系列信号事件并导致脱颗粒,包括细胞因子及趋化因子产生以及白三烯的释放.由于IgE在过敏反应中的重要作用,现在的研究主要集中在FcεRI下游的信号事件.其脱颗粒的分子机制是一个由多种蛋白质分子介导的,各个环节受到精确调控的复杂过程.对肥大细胞脱颗粒分子机制的深入研究将给过敏性疾病提供一个新的治疗方案.     

Estrogen and progesterone regulate the IL-6 signal transduction pathway in antibody secreting cells

Regulation of the immune response is necessary to allow successful pregnancy. Asymmetric IgG antibodies are involved in fetal maintenance. We have previously demonstrated that estrogen (E2) and progesterone (P4) modulate the synthesis of asymmetric antibodies but the underlying mechanisms remain unclear. Since IL-6 and a progesterone-induced blocking factor (PIBF) were shown to regulate asymmetric antibody synthesis, in this work we analyzed whether E2 and P4 were able to modulate IL-6 signal transduction pathways and the ability of P4 to induce PIBF synthesis, in hybridoma B cells was also evaluated. We found that the IL-6 treatment induced an increase in the expression of gp130 and JAK1 by the hybridoma. E2 and P4 diminished the IL-6-induced gp130 expression in a dose-dependent manner, whereas the expression of JAK1 was not significantly affected. At 10(-6)M concentration, the steroids inhibited the phosphorylation of gp130 and diminished the IL-6-induced STAT3 phosphorylation and traslocation to the nucleus. Maximal PIBF expression was observed when the hybridoma was cultured with 10(-10)M P4, compared to the control (p<0.05). Results demonstrate two molecular mechanisms, the modulation of the IL-6R signal transduction pathway and PIBF induction, which could be involved in the immunoregulatory role of sexual steroids during pregnancy.     

Agrin‐independent activation of the agrin signal transduction pathway

The neural factor agrin induces the aggregation of acetylcholine receptors (AChRs) and other synaptic molecules on cultured myotubes. This aggregating activity can be mimicked by experimental manipulations that include treatment with neuraminidase or elevated calcium. We report evidence that neuraminidase and calcium act through the agrin signal transduction pathway. The effects of neuraminidase and calcium on AChR clustering are additive with that of agrin at low concentrations and cosaturating at high concentrations. In addition, like agrin, both neuraminidase and calcium cause rapid tyrosine phosphorylation of the muscle‐specific kinase (MuSK) and the AChR‐β subunit. Our results argue that all three agents act directly on components of the same signal transduction complex. We suggest that sialic acids on components of the complex inhibit interactions necessary for signal transduction and that disinhibition can result in activation. In such a model, agrin could activate signal transduction by disinhibition or by circumventing the inhibition. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 356–365, 1999     

Role of the JAK/STAT signal transduction pathway in the regulation of gene expression in CNS

Over the last 20 years the JAK/STAT signal transduction pathway has been extensively studied. An enormous amount of data on different cell signal transduction pathways is now available. The JAK/STAT signal transduction pathway is one of the intracellular signaling pathways activated by cytokines and growth factors that was first studied in the hematopoietic system, but recent data demonstrate that this signal transduction is also greatly utilized by other systems. The JAK/STAT pathway is a signaling cascade that links the activation of specific cell membrane receptors to nuclear gene expression. This review is focused on the role of JAK/STAT signal transduction pathway activation in the central nervous system (CNS).     

Mathematical modeling and sensitivity analysis of G1/S phase in the cell cycle including the DNA-damage signal transduction pathway

The cell cycle has checkpoint systems, which control G1/S, G2/M and G0/G1 phase transitions. When a normal cell suffers from DNA-damage, the signal transduction of DNA-damage causes the cell cycle arrest by using the checkpoint systems. Therefore, the elucidation of interaction between the signal transduction of DNA-damage and the checkpoint systems is an important problem. In this study, we constructed a novel mathematical model (proposed model) which integrated G1/S-checkpoint model with a signal transduction of DNA damage model and performed some numerical simulations. The proposed model realized some biological findings of G1/S phase with or without DNA-damage, which suggested that proposed model is biologically appropriate. Moreover, the results of sensitivity analysis of the proposed model indicated the predominant factors of G1/S phase and some factors concerned with the transformation of cells.     

Gene regulation and signal transduction in the immune system

A report of the meeting 'Gene Expression and Signaling in the Immune System', Cold Spring Harbor, USA, 22-26 April 2008.     

Gac/Rsm signal transduction pathway of γ-proteobacteria: from RNA recognition to regulation of social behaviour

In many γ-proteobacteria, the conserved GacS/GacA (BarA/UvrY) two-component system positively controls the expression of one to five genes specifying small RNAs (sRNAs) that are characterized by repeated unpaired GGA motifs but otherwise appear to belong to several independent families. The GGA motifs are essential for binding small, dimeric RNA-binding proteins of a single conserved family designated RsmA (CsrA). These proteins, which also occur in bacterial species outside the γ-proteobacteria, act as translational repressors of certain mRNAs when these contain an RsmA/CsrA binding site at or near the Shine-Dalgarno sequence plus additional binding sites located in the 5' untranslated leader mRNA. Recent structural data have established that the RsmA-like protein RsmE of Pseudomonas fluorescens makes specific contacts with an RNA consensus sequence 5'-^A/_UCANGGANG^U/_A-3' (where N is any nucleotide). Interaction with an RsmA/CsrA protein promotes the formation of a short stem supporting an ANGGAN loop. This conformation hinders access of 30S ribosomal subunits and hence translation initiation. The output of the Gac/Rsm cascade varies widely in different bacterial species and typically involves management of carbon storage and expression of virulence or biocontrol factors. Unidentified signal molecules co-ordinate the activity of the Gac/Rsm cascade in a cell population density-dependent manner.     

Effect of hyperthermia in combination with TRAIL on the JNK‐Bim signal transduction pathway and growth of xenograft tumors

Approximately 25% of patients with colorectal cancer develop metastases to the liver, and surgery is currently the best treatment available. But there are several patients who are unresectable, and isolated hepatic perfusion (IHP) offers a different approach in helping to treat these patients. IHP is a method used for isolating the liver and delivering high doses of chemotherapeutic agents. The efficacy of IHP has been improved by combining hyperthermia not only with chemotherapeutics but with other deliverable agents such as tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL). In this study, we used human colorectal cancer CX‐1 cells and treated them with hyperthermia and TRAIL, causing cytotoxicity. We were able to demonstrate that the numbers of live cells were significantly reduced with hyperthermia and 10 ng/ml of TRAIL combined. We also showed that the effect of hyperthermia on TRAIL in our studies was enhancement of the apoptotic pathway by the promotion of JNK and Bim_EL activity as well as PARP cleavage. We have also used our CX‐1 cells to generate tumors in Balb/c nude mice. With intratumoral injections of TRAIL combined with hyperthermia at 42°C, we were able to show a delayed onset of tumor growth in our xenograft model. J. Cell. Biochem. 110: 1073–1081, 2010. Published 2010 Wiley‐Liss, Inc.