Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12B
pubmed:dateCreated
1991-3-14
pubmed:abstractText
Using site-directed mutagenesis of a PDGF-A cDNA clone, we identify two domains that are required to generate stable, mitogenically active PDGF-AA homodimers. Alteration of the tetra-basic amino acid sequence (Arg84-Arg-Lys-Arg to Arg-Ser-Asn-Gly) results in the formation of stable pro-PDGF-A homodimers that lack mitogenic activity. Substitution of serine for Cys129 destabilizes PDGF-A subunits within the cell. Genes incorporating either the processing lesion or the cysteine substitution suppress wild-type PDGF-A gene expression in a trans-dominant fashion. Suppression occurs because the mutant PDGF subunits dimerize with wild-type subunits to form inactive or unstable heterodimers. Suppression is exerted across phylogenetic boundaries; thus, the mouse PDGF-A chain mutants inhibit the activity of the wild-type Xenopus PDGF-A. The cysteine mutant gene suppresses expression of PDGF-B (c-sis), as well as PDGF-A. The processing mutant gene, however, suppresses only PDGF-A. Dominant-negative mutations of PDGF and other growth factors which, like PDGF, function as dimers may prove useful for creating animals models of growth factor deficiency disease states and for revealing the function of growth factors during early embryonic development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0890-9369
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2333-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Dominant-negative mutants of a platelet-derived growth factor gene.
pubmed:affiliation
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't