|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0022984,
umls-concept:C0033684,
umls-concept:C0206364,
umls-concept:C0332255,
umls-concept:C0444626,
umls-concept:C1414991,
umls-concept:C1514562,
umls-concept:C1707271,
umls-concept:C1879547,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
|
|
pubmed:issue |
46
|
|
pubmed:dateCreated |
2002-11-11
|
|
pubmed:abstractText |
Receptor tyrosine kinases of the Axl family are activated by Gas6, the product of growth arrest-specific gene 6. Gas6-Axl signaling is implicated in cell survival, adhesion, and migration. The receptor-binding site of Gas6 is located within a C-terminal pair of laminin G-like (LG) domains that do not resemble any other receptor tyrosine kinase ligand. We report the crystal structure at 2.2-A resolution of a Gas6 fragment spanning both LG domains (Gas6-LG). The structure reveals a V-shaped arrangement of LG domains strengthened by an interdomain calcium-binding site. LG2 of Gas6-LG contains two unusual features: an alpha-helix cradled by one edge of the LG beta-sandwich and a conspicuous patch of surface-exposed hydrophobic residues. Mutagenesis of some residues in this patch reduces Gas6-LG binding to the extracellular domain of Axl as well as Axl activation in glioblastoma cells, identifying a component of the receptor-binding site of Gas6.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
277
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
44164-70
|
|
pubmed:dateRevised |
2010-4-26
|
|
pubmed:meshHeading |
pubmed-meshheading:12218057-Amino Acid Sequence,
pubmed-meshheading:12218057-Binding Sites,
pubmed-meshheading:12218057-Calcium,
pubmed-meshheading:12218057-Crystallography, X-Ray,
pubmed-meshheading:12218057-Culture Media, Serum-Free,
pubmed-meshheading:12218057-DNA, Complementary,
pubmed-meshheading:12218057-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:12218057-Humans,
pubmed-meshheading:12218057-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12218057-Laminin,
pubmed-meshheading:12218057-Ligands,
pubmed-meshheading:12218057-Models, Molecular,
pubmed-meshheading:12218057-Molecular Sequence Data,
pubmed-meshheading:12218057-Mutagenesis, Site-Directed,
pubmed-meshheading:12218057-Protein Binding,
pubmed-meshheading:12218057-Protein Structure, Tertiary,
pubmed-meshheading:12218057-Proteins,
pubmed-meshheading:12218057-Sequence Homology, Amino Acid,
pubmed-meshheading:12218057-Tumor Cells, Cultured
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains.
|
|
pubmed:affiliation |
Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
