WazAMG

WazAMG

  • Member since: 3/11/2012
 
 
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  1. Hello Waz, i don t know if you will be very happy ... but please (smiley ) could you have a look for the english language ?  i promise you belgian chocolates if you take some time this week (another smiley ) Thank You

  2. Ragulator is a pentameric complex involved in the regulation of mTORC1.
    Liron Bar-Peled,1,2 Lawrence D. Schweitzer,1,2 Roberto Zoncu,1,2 and David M. Sabatini1,2,3,*
    1Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center,
    Cambridge, MA 02142, USA
    2Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    3Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    *Correspondence: sabatini@wi.mit.edu

    The mechanistic target of rapamycine complex I (mTORC1) is an enzyme of the serine threonine kinase family involved in growth-promoting functions (Kim DH. Et al 2002; reviewed In Howell and Manning 2011). The regulation of its activity implicate either the tuberous sclerosis heterodimer (TSC1-TSC2) a GTPase activating protein (GAP) for Rheb1 or an independent way recently approached based on the capacity of the amino acid to induce the translocation of the mTORC1 complex to lysosomal surface (Zoncu et al, 2011a) thanks to Rag GTPase. The second way required the trimeric complex called Ragulator to ferry the RagGTPase to the lysosomal surface and activate the mTORC1 complex.
    However the nature and the structure of Ragulator were only approached (Sancak et al., 2010).
    Here we have demonstrated the pentameric composition of Ragulator, its essential scaffold role for RagGTPase and have approached the way by which amino acids regulate the mTORC1 pathway.
    We found in cells free assays that Ragulator was a pentameric complex compounded by two more protein: HBXIP and C7orf59. These new proteins interact highly with RagB from the RagGTPase and the entire pentameric complex is essential for the activation of the RagGTPase. Inactivation of the expression of either HBXIP or C7org59 leads us to the conclusion that Ragulator acts as a scaffold for the RagGTPase. The contribution of amino acids to this way is expressed by a strengthening of the bind RagGTPase-Ragulator in starvation conditions.
    Our results confirm the important implication of Ragulator for mTORC1 so much for the activation of this complex as for its translocation until the lysosomal surface.
    We anticipate our outcomes to be a starting point for deeper investigations on the function of Ragulator.

  3. Hello Waz,                     big epidemic of reset again ^,^
    Be careful

  4. Hi, AMG,

    may I ask if you know user Grandmama? Do you often play with him/her? Hoestly, what is you opinion to him/her? Thanks.
    Eneolit