Linked Life Data

3305909

Source:http://linkedlifedata.com/resource/pubmed/id/3305909

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-4
pubmed:dateCreated
1987-10-22
pubmed:abstractText
The epidermal growth factor receptor (EGFR) and insulin receptor undergo slow post-translational modification by which they acquire hormone binding and tyrosine kinase (EGFR) function. The half-time for acquisition of EGF or insulin binding activity is 30-40 min and of tyrosine kinase activity (EGFR), is 10-15 min. Tunicamycin, an inhibitor of N-linked oligosaccharide addition, blocks acquisition of both EGF and insulin binding activity. With EGFR, activation precedes acquisition of resistance to endoglucosaminidase H (t1/2 approximately equal to 75 min), a medial Golgi event. Treatment of active high mannose receptor with endo H generates fully active aglyco-receptor; thus, core oligosaccharide addition is a prerequisite for activation, but not for EGF binding per se. EGFR is activated in and translocated from the endoplasmic reticulum (ER) slowly (t1/2 approximately equal to 75 min). Since translocation rate equals the rate for acquisition of endo H resistance, transit from the ER is rate limiting for EGFR maturation. Tunicamycin inhibits exit from the ER parallel to its effect on acquisition of binding activity. Insulin proreceptor, a 210 kDa high-mannose glycopolypeptide, acquires insulin binding function (t1/2 approximately equal to 45 min) then is proteolytically cleaved (t1/2 approximately equal to 3 hr) into subunits of the mature alpha 2 beta 2 receptor. Modification giving rise to insulin binding activity is due to a conformational change in the binding domain, since human autoimmune antibody recognizes only the active species, while rabbit polyclonal antibody recognizes all forms. Newly-translated EGF proreceptor lacks a functional tyrosine domain capable of autophosphorylation; 30-40 min after translation, while still in the ER, tyrosine kinase activity is acquired. Since the kinase domain is cytoplasmic, the receptor may become phosphorylated on tyrosine before reaching the plasma membrane.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0197-5110
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
321-54
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:3305909-Adipose Tissue, pubmed-meshheading:3305909-Binding Sites, pubmed-meshheading:3305909-Carcinoma, Squamous Cell, pubmed-meshheading:3305909-Cell Line, pubmed-meshheading:3305909-Endoplasmic Reticulum, pubmed-meshheading:3305909-Epidermal Growth Factor, pubmed-meshheading:3305909-Glycoproteins, pubmed-meshheading:3305909-Humans, pubmed-meshheading:3305909-Insulin, pubmed-meshheading:3305909-Kinetics, pubmed-meshheading:3305909-Models, Biological, pubmed-meshheading:3305909-Phosphorylation, pubmed-meshheading:3305909-Protein Binding, pubmed-meshheading:3305909-Protein Conformation, pubmed-meshheading:3305909-Protein Processing, Post-Translational, pubmed-meshheading:3305909-Protein-Tyrosine Kinases, pubmed-meshheading:3305909-Receptor, Epidermal Growth Factor, pubmed-meshheading:3305909-Receptor, Insulin, pubmed-meshheading:3305909-Tunicamycin
pubmed:year
1987
pubmed:articleTitle
Post-translational acquisition of ligand binding- and tyrosine kinase-domain function by the epidermal growth factor and insulin receptors.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't