Linked Life Data

17995453

Source:http://linkedlifedata.com/resource/pubmed/id/17995453

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-12-20
pubmed:abstractText
AS160 (Akt substrate of 160 kDa) and TBC1D1 are related RabGAPs (Rab GTPase-activating proteins) implicated in regulating the trafficking of GLUT4 (glucose transporter 4) storage vesicles to the cell surface. All animal species examined contain TBC1D1, whereas AS160 evolved with the vertebrates. TBC1D1 has two clusters of phosphorylated residues, either side of the second PTB (phosphotyrosine-binding domain). Each cluster contains a 14-3-3-binding site. When AMPK (AMP-activated protein kinase) is activated in HEK (human embryonic kidney)-293 cells, 14-3-3s bind primarily to pSer237 (where pSer is phosphorylated serine) in TBC1D1, whereas 14-3-3 binding depends primarily on pThr596 (where pThr is phosphorylated threonine) in cells stimulated with IGF-1 (insulin-like growth factor 1), EGF (epidermal growth factor) and PMA; and both pSer237 and pThr596 contribute to 14-3-3 binding in cells stimulated with forskolin. In HEK-293 cells, LY294002 inhibits phosphorylation of Thr596 of TBC1D1, and promotes phosphorylation of AMPK and Ser237 of TBC1D1. In vitro phosphorylation experiments indicated regulatory interactions among phosphorylated sites, for example phosphorylation of Ser235 prevents subsequent phosphorylation of Ser237. In rat L6 myotubes, endogenous TBC1D1 is strongly phosphorylated on Ser237 and binds to 14-3-3s in response to the AMPK activators AICAR (5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside), phenformin and A-769662, whereas insulin promotes phosphorylation of Thr596 but not 14-3-3 binding. In contrast, AS160 is phosphorylated on its 14-3-3-binding sites (Ser341 and Thr642) and binds to 14-3-3s in response to insulin, but not A-769662, in L6 cells. These findings suggest that TBC1D1 and AS160 may have complementary roles in regulating vesicle trafficking in response to insulin and AMPK-activating stimuli in skeletal muscle.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
409
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
449-59
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17995453-AMP-Activated Protein Kinases, pubmed-meshheading:17995453-Animals, pubmed-meshheading:17995453-Binding Sites, pubmed-meshheading:17995453-GTPase-Activating Proteins, pubmed-meshheading:17995453-Humans, pubmed-meshheading:17995453-Immunohistochemistry, pubmed-meshheading:17995453-Insulin, pubmed-meshheading:17995453-Insulin-Like Growth Factor I, pubmed-meshheading:17995453-Multienzyme Complexes, pubmed-meshheading:17995453-Muscle Fibers, Skeletal, pubmed-meshheading:17995453-Mutation, pubmed-meshheading:17995453-Nuclear Proteins, pubmed-meshheading:17995453-Phosphorylation, pubmed-meshheading:17995453-Phylogeny, pubmed-meshheading:17995453-Protein-Serine-Threonine Kinases, pubmed-meshheading:17995453-Rats, pubmed-meshheading:17995453-Serine, pubmed-meshheading:17995453-Threonine
pubmed:year
2008
pubmed:articleTitle
Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators.
pubmed:affiliation
MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't