Linked Life Data

21303927

Source:http://linkedlifedata.com/resource/pubmed/id/21303927

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 5
pubmed:dateCreated
2011-2-15
pubmed:abstractText
Insulin signaling comprises a complex cascade of events, playing a key role in the regulation of glucose metabolism and cellular growth. Impaired response to insulin is the hallmark of diabetes, whereas upregulated insulin activity occurs in many cancers. Two splice variants of the insulin receptor (IR) exist in mammals: IR-A, lacking exon 11, and full-length IR-B. Although considerable biochemical data exist on insulin binding and downstream signaling, little is known about the dynamics of the IR itself. We created functional IR transgenes fused with visible fluorescent proteins for use in combination with biotinamido-caproyl insulin and streptavidin quantum dots. Using confocal and structured illumination microscopy, we visualized the endocytosis of both isoforms in living and fixed cells and demonstrated a higher rate of endocytosis of IR-A than IR-B. These differences correlated with higher and sustained activation of IR-A in response to insulin and with distinctive ERK1/2 activation profiles and gene transcription regulation. In addition, cells expressing IR-B showed higher AKT phosphorylation after insulin stimulation than cells expressing IR-A. Taken together, these results suggest that IR signaling is dependent on localization; internalized IRs regulate mitogenic activity, whereas metabolic balance signaling occurs at the cell membrane.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1477-9137
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
801-11
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21303927-Alternative Splicing, pubmed-meshheading:21303927-Cell Membrane, pubmed-meshheading:21303927-Endocytosis, pubmed-meshheading:21303927-Enzyme Activation, pubmed-meshheading:21303927-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:21303927-HeLa Cells, pubmed-meshheading:21303927-Humans, pubmed-meshheading:21303927-Insulin, pubmed-meshheading:21303927-Protein Isoforms, pubmed-meshheading:21303927-Proto-Oncogene Proteins c-akt, pubmed-meshheading:21303927-Pseudopodia, pubmed-meshheading:21303927-Quantum Dots, pubmed-meshheading:21303927-Receptor, Insulin, pubmed-meshheading:21303927-Recombinant Fusion Proteins, pubmed-meshheading:21303927-Signal Transduction, pubmed-meshheading:21303927-Transcription Factor AP-1, pubmed-meshheading:21303927-Transgenes
pubmed:year
2011
pubmed:articleTitle
Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B.
pubmed:affiliation
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CIHIDECAR, CONICET, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Buenos Aires, Argentina.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't