|
|
By admin, on May 16th, 2012
J Neurosci. 2012 May 9; 32(19): 6587-6599
Takano T, Tomomura M, Yoshioka N, Tsutsumi K, Terasawa Y, Saito T, Kawano H, Kamiguchi H, Fukuda M, Hisanaga SI
Axonal outgrowth is a coordinated process of cytoskeletal dynamics and membrane trafficking; however, little is known about proteins responsible for regulating the membrane supply. LMTK1 (lemur kinase 1)/AATYK1 (apoptosis-associated tyrosine kinase 1) is a serine/threonine kinase that is highly expressed in neurons. We recently reported that LMTK1 plays a role in recycling endosomal trafficking in CHO-K1 cells. Here we explore the role of LMTK1 in axonal outgrowth and its regulation by Cdk5 using mouse brain cortical neurons. LMTK1 was expressed and was phosphorylated at Ser34, the Cdk5 phosphorylation site, at the time of axonal outgrowth in culture and colocalized with Rab11A, the small GTPase that regulates recycling endosome traffic, at the perinuclear region and in the axon. Overexpression of the unphosphorylated mutant LMTK1-S34A dramatically promoted axonal outgrowth in cultured neurons. Enhanced axonal outgrowth was diminished by the inactivation of Rab11A, placing LMTK1 upstream of Rab11A. Unexpectedly, the downregulation of LMTK1 by knockdown or gene targeting also significantly enhanced axonal elongation. Rab11A-positive vesicles were transported anterogradely more quickly in the axons of LMTK1-deficient neurons than in those of wild-type neurons. The enhanced axonal outgrowth was reversed by LMTK1-WT or the LMTK1-S34D mutant, which mimics the phosphorylated state, but not by LMTK1-S34A. Thus, LMTK1 can negatively control axonal outgrowth by regulating Rab11A activity in a Cdk5-dependent manner, and Cdk5-LMTK1-Rab11 is a novel signaling pathway involved in axonal outgrowth.
The rest is here:
LMTK1/AATYK1 Is a Novel Regulator of Axonal Outgrowth That Acts via Rab11 in a Cdk5-Dependent Manner.
By admin, on May 15th, 2012
Open Biochem J. 2012; 6: 40-2
Contag B
A new hypothesis is discussed, which describes the initiation of the carcinogenesis through polycyclic aromatic hydrocarbons (PAHs) and aminoazo dyes (AZOs) as a two-step process: the oncogenic proteins of the ras or ras-like on-cogenes activated by mutation (“initiation A “) co-operate with the complexes in the plasma membrane formed during the “initiation B ” stage from the parent compounds of the PAHs or AZOs with cholesterol and apolipoprotein A-I. The final result of this co-operation, or the “complete initiation”, is an irreversibly modified membrane architecture with negative consequences for growth control.
Go here to read the rest:
Hypothetical two-step initiation of experimental carcinogenesis by polycyclic aromatic hydrocarbons and aminoazo dyes.
By admin, on May 13th, 2012
J Biochem. 2012 May 9;
Withanage K, Nakagawa K, Ikeda M, Kurihara H, Kudo T, Yang Z, Sakane A, Sasaki T, Hata Y
RASSF6, a member of RASSF tumor suppressor proteins, binds to mammalian Ste20-like kinases (MST1/2), core kinases of the proapoptotic Hippo pathway, and cooperates with the Hippo pathway to induce apoptosis. We originally identified RASSF6 as a putative interactor of membrane-associated guanylate kinase inverted (MAGI)-1 by the yeast two-hybrid screening. We used human kidney cDNA library for the screening. MAGI-1 is abundantly expressed in kidney and is a core component of the slit diaphragm. These findings suggest that RASSF6 is expressed in kidney. However, the function of RASSF6 in kidney is not yet studied. We performed this study to confirm the interaction of RASSF6 with MAGI-1, to analyze the expression of RASSF6 in kidney and to gain insight into the function of RASSF6 in kidney. RASSF6 binds to PDZ domains of MAGI-1 through its C-terminal PDZ-binding motif and is coimmunoprecipitated with MAGI-1 from rat liver. RASSF6 is localized in normal kidney glomerulus but disappears when the slit diaphragm is disrupted in nephrotic kidney. RASSF6 is also localized on apical membranes in renal proximal tubular epithelial cells. We demonstrated that RASSF6 as well as the Hippo pathway are involved in the sorbitol-induced apoptosis in immortalized human proximal renal tubular epithelial HK-2 cells.
See the original post here:
Expression of RASSF6 in kidney and the implication of RASSF6 and the Hippo pathway in the sorbitol-induced apoptosis in renal proximal tubular epithelial cells.
By admin, on May 13th, 2012
J Biochem. 2012 May 9;
Withanage K, Nakagawa K, Ikeda M, Kurihara H, Kudo T, Yang Z, Sakane A, Sasaki T, Hata Y
RASSF6, a member of RASSF tumor suppressor proteins, binds to mammalian Ste20-like kinases (MST1/2), core kinases of the proapoptotic Hippo pathway, and cooperates with the Hippo pathway to induce apoptosis. We originally identified RASSF6 as a putative interactor of membrane-associated guanylate kinase inverted (MAGI)-1 by the yeast two-hybrid screening. We used human kidney cDNA library for the screening. MAGI-1 is abundantly expressed in kidney and is a core component of the slit diaphragm. These findings suggest that RASSF6 is expressed in kidney. However, the function of RASSF6 in kidney is not yet studied. We performed this study to confirm the interaction of RASSF6 with MAGI-1, to analyze the expression of RASSF6 in kidney and to gain insight into the function of RASSF6 in kidney. RASSF6 binds to PDZ domains of MAGI-1 through its C-terminal PDZ-binding motif and is coimmunoprecipitated with MAGI-1 from rat liver. RASSF6 is localized in normal kidney glomerulus but disappears when the slit diaphragm is disrupted in nephrotic kidney. RASSF6 is also localized on apical membranes in renal proximal tubular epithelial cells. We demonstrated that RASSF6 as well as the Hippo pathway are involved in the sorbitol-induced apoptosis in immortalized human proximal renal tubular epithelial HK-2 cells.
See original here:
Expression of RASSF6 in kidney and the implication of RASSF6 and the Hippo pathway in the sorbitol-induced apoptosis in renal proximal tubular epithelial cells.
By admin, on May 11th, 2012
By admin, on May 8th, 2012
PLoS One . 2012; 7(4): e35699 Krauland MG, Dunning Hotopp JC, Riley DR, Daugherty SC, Marsh JW, Messonnier NE, Mayer LW, Tettelin H, Harrison LH In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade.
The rest is here:
Whole Genome Sequencing to Investigate the Emergence of Clonal Complex 23 Neisseria meningitidis Serogroup Y Disease in the United States.
By admin, on May 8th, 2012
PLoS One. 2012; 7(4): e36405
Torres J, Prieto J, Durupt FC, Broad S, Watt FM
The ability to direct differentiation of mouse embryonic stem (ES) cells into specific lineages not only provides new insights into the pathways that regulate lineage selection but also has translational applications, for example in drug discovery. We set out to develop a method of differentiating ES cells into mesodermal cells at high efficiency without first having to induce embryoid body formation. ES cells were plated on a feeder layer of PA6 cells, which have membrane-associated stromal-derived inducing activity (SDIA), the molecular basis of which is currently unknown. Stimulation of ES/PA6 co-cultures with Bone Morphogenetic Protein 4 (BMP4) both favoured self-renewal of ES cells and induced differentiation into a Desmin and Nestin double positive cell population. Combined stimulation with BMP4 and all-trans Retinoic Acid (RA) inhibited self-renewal and resulted in 90% of cells expressing Desmin and Nestin. Quantitative reverse transcription-polymerase chain reaction (qPCR) analysis confirmed that the cells were of mesodermal origin and expressed markers of mesenchymal and smooth muscle cells. BMP4 activation of a MAD-homolog (Smad)-dependent reporter in undifferentiated ES cells was attenuated by co-stimulation with RA and co-culture with PA6 cells. The Notch ligand Jag1 was expressed in PA6 cells and inhibition of Notch signalling blocked the differentiation inducing activity of PA6 cells. Our data suggest that mesodermal differentiation is regulated by the level of Smad activity as a result of inputs from BMP4, RA and the Notch pathway.
Excerpt from:
Efficient Differentiation of Embryonic Stem Cells into Mesodermal Precursors by BMP, Retinoic Acid and Notch Signalling.
By admin, on May 6th, 2012
By admin, on May 5th, 2012
Oncol Rep. 2012 Apr 30;
Solár P, Hrčková G, Varinská L, Solárová Z, Kriška J, Uhrínová I, Kello M, Mojžiš J, Fedoročko P, Sytkowski AJ
Erythropoietin (Epo) is a critical regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of a recombinant protein, it is widely used to treat various forms of anemia, including that associated with cancer and with the myelosuppressive effects of chemotherapy. Studies of ovarian cancer cell lines have demonstrated the presence of the Epo receptor (EpoR), but there are disagreements regarding its localization and functionality in these cells. Using fluorescence microscopy, we were not able to identify the EpoR on the surface of A2780 cells, in contrast to the positive control K562 cells. Flow cytometry did reveal a weak surface EpoR signal in A2780 cells. Interestingly, most of the EpoR in A2780 cells was found in the cytoplasm, more abundantly as an intracellular membrane-associated protein than a soluble one. Silencing EpoR expression by lentiviral-mediated shRNA resulted in reduced A2780 prolife-ration as well as reduction in Epo-induced phosphorylation of Erk1/2. Our findings provide important insights into the biology of the EpoR in ovarian cancer cells.
Read the original here:
Location and the functionality of erythropoietin receptor(s) in A2780 cells.
By admin, on May 4th, 2012
Integral Molecular Announces Patent Allowance for its Membrane Protein Lipoparticle Technology. … (Nanowerk News) Integral Molecular, a leader in membrane protein reagents and services, announces the issuance of a key patent protecting its methodology for generating Lipoparticles, which provide highly-concentrated membrane proteins in their native conformation for antibody and drug discovery applications focused on membrane protein targets such as G …
Continued here:
Integral Molecular Announces Patent Allowance for its Membrane …
By admin, on May 4th, 2012
Integral Molecular Announces Patent Allowance for its Membrane Protein Lipoparticle Technology. … (Nanowerk News) Integral Molecular, a leader in membrane protein reagents and services, announces the issuance of a key patent protecting its methodology for generating Lipoparticles, which provide highly-concentrated membrane proteins in their native conformation for antibody and drug discovery applications focused on membrane protein targets such as G …
See the rest here:
Integral Molecular Announces Patent Allowance for its Membrane …
By admin, on May 3rd, 2012
By admin, on May 3rd, 2012
By admin, on May 3rd, 2012
By admin, on May 3rd, 2012
By admin, on May 3rd, 2012
|
