Linked Life Data

9178769

Source:http://linkedlifedata.com/resource/pubmed/id/9178769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1997-7-3
pubmed:databankReference
pubmed:abstractText
The c-Cbl proto-oncogene encodes a multidomain phosphoprotein that has been demonstrated to interact with a wide range of signalling proteins. The biochemical function of c-Cbl in these complexes is, however, unclear. Recent studies with the C. elegans Cbl homologue, sli-1, have suggested that Cbl proteins may act as negative regulators of EGF receptor (EGFR) signalling. As the EGFR and other protein tyrosine kinase receptor signalling pathways are highly conserved between insects and vertebrates, we sought a Drosophila homologue of c-Cbl for a detailed genetic analysis. We report here that Drosophila melanogaster has a single gene, D-cbl, that is homologous to c-cbl. We find that D-cbl encodes a 52 kDa protein that has a high degree of similarity to c-Cbl and SLI-1 across novel phosphotyrosine-binding (PTB) and RING finger domains. Surprisingly, however, D-Cbl is C-terminally truncated relative to c-Cbl and SLI-1 and consequently is unable to bind SH3-domain containing adaptor proteins, including the Drosophila Grb2 homologue, Drk. Although the D-Cbl protein lacks Drk binding sites it can nevertheless associate with a tyrosine phosphorylated protein, or is itself tyrosine phosphorylated in an DER dependent manner and associates with activated Drosophila EGF receptors (DER) in vivo. Consistent with a role for D-Cbl in DER dependent patterning in the embryo and adult, D-Cbl is expressed at a high level in early embryos and throughout the imaginal discs in third instar larvae. This study forms the basis for future genetic analysis of D-Cbl, aimed at gaining insights into the role of Cbl proteins in signal transduction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2709-19
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9178769-Amino Acid Sequence, pubmed-meshheading:9178769-Animals, pubmed-meshheading:9178769-Base Sequence, pubmed-meshheading:9178769-Binding Sites, pubmed-meshheading:9178769-DNA, Complementary, pubmed-meshheading:9178769-Drosophila Proteins, pubmed-meshheading:9178769-Drosophila melanogaster, pubmed-meshheading:9178769-Evolution, Molecular, pubmed-meshheading:9178769-Gene Expression Regulation, Developmental, pubmed-meshheading:9178769-Humans, pubmed-meshheading:9178769-Molecular Sequence Data, pubmed-meshheading:9178769-Proto-Oncogene Proteins, pubmed-meshheading:9178769-Proto-Oncogene Proteins c-cbl, pubmed-meshheading:9178769-Receptor, Epidermal Growth Factor, pubmed-meshheading:9178769-Sequence Homology, Amino Acid, pubmed-meshheading:9178769-Ubiquitin-Protein Ligases
pubmed:year
1997
pubmed:articleTitle
D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites.
pubmed:affiliation
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne VIC, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't