rdf:type |
|
lifeskim:mentions |
umls-concept:C0007603,
umls-concept:C0036536,
umls-concept:C0036537,
umls-concept:C0040715,
umls-concept:C0127400,
umls-concept:C0380603,
umls-concept:C0439851,
umls-concept:C0599718,
umls-concept:C0599813,
umls-concept:C0599893,
umls-concept:C1512977,
umls-concept:C1522702,
umls-concept:C1552596,
umls-concept:C1947931
|
pubmed:issue |
8
|
pubmed:dateCreated |
2004-2-17
|
pubmed:abstractText |
Fibroblast growth factor 2 (FGF-2) is a pro-angiogenic mediator that is secreted by both normal and neoplastic cells. Intriguingly, FGF-2 has been shown to be exported by an endoplasmic reticulum/Golgi-independent pathway; however, the molecular machinery mediating this process has remained elusive. Here we introduce a novel in vitro system that functionally reconstitutes FGF-2 secretion. Based on affinity-purified plasma membrane inside-out vesicles, we demonstrate post-translational membrane translocation of FGF-2 as shown by protease protection experiments. This process is blocked at low temperature but apparently does not appear to be driven by ATP hydrolysis. FGF-2 membrane translocation occurs in a unidirectional fashion requiring both integral and peripheral membrane proteins. These findings provide direct evidence that FGF-2 secretion is based on its direct translocation across the plasma membrane of mammalian cells. When galectin-1 and macrophage migration inhibitory factor, other proteins exported by unconventional means, were analyzed for translocation into plasma membrane inside-out vesicles, galectin-1 was found to be transported as efficiently as FGF-2. By contrast, migration inhibitory factor failed to traverse the membrane of inside-out vesicles. These findings establish the existence of multiple distinct secretory routes that are operational in the absence of a functional endoplasmic reticulum/Golgi system.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0021-9258
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
20
|
pubmed:volume |
279
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
6244-51
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:14645213-Adenosine Triphosphate,
pubmed-meshheading:14645213-Animals,
pubmed-meshheading:14645213-Antigens, CD8,
pubmed-meshheading:14645213-CHO Cells,
pubmed-meshheading:14645213-Cell Membrane,
pubmed-meshheading:14645213-Cricetinae,
pubmed-meshheading:14645213-Cytosol,
pubmed-meshheading:14645213-Detergents,
pubmed-meshheading:14645213-Endoplasmic Reticulum,
pubmed-meshheading:14645213-Fibroblast Growth Factor 2,
pubmed-meshheading:14645213-Galectin 1,
pubmed-meshheading:14645213-Golgi Apparatus,
pubmed-meshheading:14645213-Hydrolysis,
pubmed-meshheading:14645213-Macrophage Migration-Inhibitory Factors,
pubmed-meshheading:14645213-Microscopy, Electron,
pubmed-meshheading:14645213-Models, Biological,
pubmed-meshheading:14645213-Protein Transport,
pubmed-meshheading:14645213-Sodium Dodecyl Sulfate,
pubmed-meshheading:14645213-Temperature,
pubmed-meshheading:14645213-Time Factors
|
pubmed:year |
2004
|
pubmed:articleTitle |
Unconventional secretion of fibroblast growth factor 2 is mediated by direct translocation across the plasma membrane of mammalian cells.
|
pubmed:affiliation |
Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|