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981.
Targeted deletion of protein kinase C lambda reveals a distribution of functions between the two atypical protein kinase C isoforms 总被引:1,自引:0,他引:1
Soloff RS Katayama C Lin MY Feramisco JR Hedrick SM 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(5):3250-3260
Protein kinase C lambda (PKClambda) is an atypical member of the PKC family of serine/threonine kinases with high similarity to the other atypical family member, PKCzeta. This similarity has made it difficult to determine specific roles for the individual atypical isoforms. Both PKClambda and PKCzeta have been implicated in the signal transduction, initiated by mediators of innate immunity, that culminates in the activation of MAPKs and NF-kappaB. In addition, work from invertebrates shows that atypical PKC molecules play a role in embryo development and cell polarity. To determine the unique functions of PKClambda, mice deficient for PKClambda were generated by gene targeting. The ablation of PKClambda results in abnormalities early in gestation with lethality occurring by embryonic day 9. The role of PKClambda in cytokine-mediated cellular activation was studied by making mouse chimeras from PKClambda-deficient embryonic stem cells and C57BL/6 or Rag2-deficient blastocysts. Cell lines derived from these chimeric animals were then used to dissect the role of PKClambda in cytokine responses. Although the mutant cells exhibited alterations in actin stress fibers and focal adhesions, no other phenotypic differences were noted. Contrary to experiments using dominant interfering forms of PKClambda, mutant cells responded normally to TNF, serum, epidermal growth factor, IL-1, and LPS. In addition, no abnormalities were found in T cell development or T cell activation. These data establish that, in vertebrates, the two disparate functions of atypical PKC molecules have been segregated such that PKCzeta mediates signal transduction of the innate immune system and PKClambda is essential for early embryogenesis. 相似文献
982.
983.
Interaction between the polyol pathway and non-enzymatic glycation on aortic smooth muscle cell migration and monocyte adhesion 总被引:5,自引:0,他引:5
We investigated for the interaction between the polyol pathway and enhanced non-enzymatic glycation, both implicated in the pathogenesis of diabetic atherosclerosis, in the activation of aortic smooth muscle cell (SMC) function. Mouse aortas and primary cultures of SMCs from wildtype (WT) mice and transgenic (TG) mice expressing human aldose reductase (AR) were studied regarding changes in AR activity, and SMC gene activation, migration and monocyte adhesion, in response to advanced glycation end-product modified BSA (AGE-BSA). Results showed that AGE-BSA increased AR activity in both WT and TG aortas, with greater increments (p < 0.05) in TG aortas which, basally, had elevated AR activity (2.8 fold of WT). These increments were attenuated by zopolrestat, an AR inhibitor. Similar AGE-induced increments in AR activity were observed in primary cultures of aortic SMCs from WT and TG mice (60% and 100%, respectively, P < 0.01). Such increments were accompanied by increases in intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) mRNA levels (both P < 0.05), activation of membrane-associated PKC-beta1 (P < 0.05) as well as increased SMC migration and Tamm-Horsfall protein (THP)-1 monocyte adhesion to SMCs (both p < 0.01), with all changes being significantly greater in TG SMCs (P < 0.05) and suppressible by either zopolrestat or transfection with an AR antisense oligonucleotide. Our findings suggest that the effects of AGEs on SMC activation, migration and monocyte adhesion are mediated partly through the polyol pathway and, possibly, PKC activation. The greater AGE-induced changes in the TG SMCs have provided further support for the dependency of such changes on polyol pathway hyperactivity. 相似文献
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985.
The GTPase elongation factor (EF)-G is responsible for promoting the translocation of the messenger RNA-transfer RNA complex on the ribosome, thus opening up the A site for the next aminoacyl-tRNA. Chemical modification and cryo-EM studies have indicated that tRNAs can bind the ribosome in an alternative 'hybrid' state after peptidyl transfer and before translocation, though the relevance of this state during translation elongation has been a subject of debate. Here, using pre-steady-state kinetic approaches and mutant analysis, we show that translocation by EF-G is most efficient when tRNAs are bound in a hybrid state, supporting the argument that this state is an authentic intermediate during translation. 相似文献
986.
Gérard Coureaud Rachel Charra Frédérique Datiche Charlotte Sinding Thierry Thomas-Danguin Solène Languille Bernard Hars Benoist Schaal 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(10):779-790
Birth is part of a continuum and is a major developmental change. Newborns need to adapt rapidly to the environment in terms
of physiology and behaviour, and ability to locate the maternal source of milk is vital. Mechanisms have evolved resulting
in the emission of olfactory cues by the mother and the processing of these cues by the young. Here, we focus on some sensory,
cognitive and behavioural strategies developed by the European rabbit (Oryctolagus cuniculus) that optimize the early development of offspring. In this species, chemosensory communication between the mother and young
plays a critical role in eliciting adaptive neonatal responses. In particular, lactating females release a molecule, the mammary
pheromone, which has several functional impacts. It triggers orocephalic responses involved in the quick localization of nipples
and sucking. Moreover, this unconditioned signal promotes rapid appetitive learning of novel odorants, acting as a potent
organizer of neonatal cognition. The mammary-pheromone-induced odour memory requires consolidation/reconsolidation processes
to be maintained in the long term. Finally, as this mode of conditioning also promotes learning of mixtures of odorants, it
supports investigations related to the capacity of neonatal olfaction to extract biological value from the complex environment. 相似文献
987.
Gal Markel Rona Ortenberg Rachel Seidman Sivan Sapoznik Nira Koren-Morag Michal J. Besser Jair Bar Ronnie Shapira Adva Kubi Gil Nardini Ariel Tessone Avraham J. Treves Eyal Winkler Arie Orenstein Jacob Schachter 《Cancer immunology, immunotherapy : CII》2010,59(2):215-230
It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(?) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms. 相似文献
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