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In animals, the protein kinase C (PKC) family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10), with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of PKN2 in endothelial cells or the developing heart. In contrast, inducible systemic deletion of PKN2 after E7 provoked collapse of the embryonic mesoderm. Furthermore, mouse embryonic fibroblasts, which arise from the embryonic mesoderm, depend on PKN2 for proliferation and motility. These cellular defects are reflected in vivo as dependence on PKN2 for mesoderm proliferation and neural crest migration. We conclude that failure of the mesoderm to expand in the absence of PKN2 compromises cardiovascular integrity and development, resulting in lethality.

The estrogen-related receptor (ERR) gene is a member of the nuclear receptor subfamily. Previous studies have indicated that ERR plays important roles in regulating insect growth and development. How ERR is associated with ant caste specificities remains unclear. In this study, we attempted to identify the role of ERR in the regulation of different adult caste specificities of Polyrhachis vicina Roger. Significant variations were detected in the ants including PvERR expressions, some physiological indexes and morphological traits including survival rate, body weight, body length, head width and abdominal appearance by different techniques. The results revealed that when PvERR expressions is up-regulated, boundaries of the abdominal segments were indistinct on the ventral side of the abdomen in males. Down-regulation of PvERR expressions caused abdominal swelling in males and a distended ventral abdomen in females and workers. Variation in PvERR expressions led to a remarkable decline in ant survival rates, particularly for males. These results indicated that different caste adults appeared to have different degrees of sensitivity in physiological response and morphological changes caused by variation in PvERR expressions. Thus, our data demonstrate that PvERR plays an important role in regulating the different adult caste specificities of P. vicina. [ABSTRACT FROM AUTHOR]

Summary In animals, the protein kinase C (PKC) family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10), with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of PKN2 in endothelial cells or the developing heart. In contrast, inducible systemic deletion of PKN2 after E7 provoked collapse of the embryonic mesoderm. Furthermore, mouse embryonic fibroblasts, which arise from the embryonic mesoderm, depend on PKN2 for proliferation and motility. These cellular defects are reflected in vivo as dependence on PKN2 for mesoderm proliferation and neural crest migration. We conclude that failure of the mesoderm to expand in the absence of PKN2 compromises cardiovascular integrity and development, resulting in lethality. [ABSTRACT FROM AUTHOR]

We know surprisingly little about the sex differences in the neurobiology of cocaine addiction, except females are more susceptible to the rewarding effects of cocaine than their male counterparts. Only a handful of recent studies have examined the neurobiology of cocaine-induced conditioned place preference (CPP) memory among female rodents. We contribute to this emerging line of research by documenting sex differences in cocaine-associated memory and illustrating the underlying signaling pathways in five experiments. Rimonabant (Rim), a cannabinoid CB 1 antagonist and inverse agonist, exerted a facilitating effect for low-dose cocaine and an impairing effect for high-dose cocaine CPP memory in male mice, as in our previous study, but not in female mice. Nor did we observe the effect exist among CB 1 knockout male mice, which indicated that the CB 1 receptors played a mediating role. We also found that the metabotropic glutamate receptor 5 (mGluR5) was located in the same signaling pathway as CB 1 in male mice. To clarify the mechanisms behind the sex differences, we used ovariectomized (OVX) female mice with estradiol benzoate (EB) replacement. In the OVX female mice, we showed that Rim-alone and EB-alone, but not Rim-and-EB-combined, facilitated the low-dose cocaine CPP memory. Moreover, 4-hydroxytamoxifen (4-OHT), an estrogen receptor (ER) antagonist, blocked Rim's and EB's facilitating effect. Finally, 2-methyl-6-(phenylethynyl)pyridine (MPEP), an mGluR5 antagonist, partially blocked EB's facilitating effect. In sum, we identified sex-specific effects of Rim on cocaine-induced CPP memory and the respective signaling pathways: mGluR5-CB 1 for male mice and ER-mGluR5-CB 1 for female mice. These findings may have merits for the development of sex-specific treatment for cocaine addiction. ● Females are more susceptible to the rewarding effects of cocaine than their male counterparts. ● However, we know surprisingly little about the sex differences in the neurobiology of cocaine addiction, and only a handful of recent studies have examined the neurobiology of cocaine-induced conditioned place preference (CPP) memory among female rodents. ● We contribute to this emerging line of research by documenting sex differences in cocaine-induced CPP memory and illustrating the underlying signaling pathways. ● We identified sex-specific effects of rimonabant (Rim), a cannabinoid CB 1 antagonist and inverse agonist, on cocaine-induced CPP memory and the respective signaling pathways involving metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor (ER): mGluR5-CB 1 for male mice and ER-mGluR5-CB 1 for female mice. ● We believe this novel discovery of Rim's sex-specific signaling pathways in cocaine-associated memory may have implications for the development of sex-specific treatment for cocaine addiction. [ABSTRACT FROM AUTHOR]

Reduced COUP-TFII expression contributes to endocrine resistance in breast cancer cells. Endocrine-resistant breast cancer cells have higher NFkappa B (NFκB) activity and target gene expression. The goal of this study was to determine if COUP-TFII modulates NFκB activity. Endocrine-resistant LCC9 cells with low endogenous COUP-TFII displayed ∼5-fold higher basal NFκB activity than parental endocrine-sensitive MCF-7 breast cancer cells. Transient transfection of LCC9 cells with COUP-TFII inhibited NFκB activation and reduced NFκB target gene expression. COUP-TFII and NFκB were inversely correlated in breast cancer patient samples. Endogenous COUP-TFII coimmunoprecipitated with NFκB subunits RelB and NFκB1 in MCF-7 cells. COUP-TFII inhibited NFκB-DNA binding in vitro and impaired coactivator induced NFκB transactivation. LCC9 cells were growth-inhibited by an NFκB inhibitor and 4-hydroxytamoxifen compared to MCF-7 cells. Together these data indicate a novel role for COUP-TFII in suppression of NFκB activity and explain, in part, why decreased COUP-TFII expression results in an endocrine-resistant phenotype., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)