Linked Life Data

11061555

Source:http://linkedlifedata.com/resource/pubmed/id/11061555

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-11-15
pubmed:abstractText
Point mutations of the RET receptor tyrosine kinase are responsible for the inheritance of multiple endocrine neoplasia (MEN) type 2 syndromes and are also present in a fraction of sporadic medullary thyroid carcinomas. Somatic rearrangements of the RET gene generating the chimeric RET/papillary thyroid carcinoma (PTC) oncogenes are the predominant molecular lesions associated with papillary carcinoma, the most frequent thyroid malignancy in humans. Oncogenic mutations cause constitutive activation of the kinase function of RET, which, in turn, results in the autophosphorylation of RET tyrosine residues critical for signaling. In vitro kinase assays previously revealed six putative RET autophosphorylation sites. The aim of the present study was to assess the phosphorylation of two such residues, tyrosines 1015 and 1062 (Y1015 and Y1062), in the in vivo signaling of RET and RET-derived oncogenes. Using phosphorylated RET-specific antibodies, we demonstrate that both Y1015 and Y1062 are rapidly phosphorylated upon ligand triggering of RET. Moreover, regardless of the nature of the underlying activating mutation, the concomitant phosphorylation of Y1015 and Y1062 is a common feature of the various oncogenic RET products (MEN2A, MEN2B, and PTC). This study shows that Ab-pY1062 is a useful tool with which to detect activated RET in human tumor cells and surgical samples. Finally, the microinjection of Ab-pY1062 antibodies into living cells demonstrates that Ret/PTC1 signaling is required to maintain the mitogenesis of a human carcinoma cell line expressing the Ret/PTC1 oncoprotein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3898-907
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11061555-Amino Acid Sequence, pubmed-meshheading:11061555-Animals, pubmed-meshheading:11061555-Antibodies, Blocking, pubmed-meshheading:11061555-COS Cells, pubmed-meshheading:11061555-DNA, pubmed-meshheading:11061555-Drosophila Proteins, pubmed-meshheading:11061555-Fibroblasts, pubmed-meshheading:11061555-Humans, pubmed-meshheading:11061555-Immunohistochemistry, pubmed-meshheading:11061555-Microinjections, pubmed-meshheading:11061555-Molecular Sequence Data, pubmed-meshheading:11061555-Oncogene Proteins, pubmed-meshheading:11061555-Oncogenes, pubmed-meshheading:11061555-Phosphorylation, pubmed-meshheading:11061555-Point Mutation, pubmed-meshheading:11061555-Proto-Oncogene Proteins, pubmed-meshheading:11061555-Proto-Oncogene Proteins c-ret, pubmed-meshheading:11061555-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:11061555-Thyroid Neoplasms, pubmed-meshheading:11061555-Transfection, pubmed-meshheading:11061555-Tumor Cells, Cultured, pubmed-meshheading:11061555-Tyrosine
pubmed:year
2000
pubmed:articleTitle
Tyrosines 1015 and 1062 are in vivo autophosphorylation sites in ret and ret-derived oncoproteins.
pubmed:affiliation
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto Nazionale dei Tumori di Napoli, Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.