Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway

Citation
H. Miao et al., Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway, NAT CELL BI, 3(5), 2001, pp. 527-530
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
NATURE CELL BIOLOGY
ISSN journal
1465-7392 → ACNP
Volume
3
Issue
5
Year of publication
2001
Pages
527 - 530
Database
ISI
SICI code
1465-7392(200105)3:5<527:AOERTK>2.0.ZU;2-Z
Abstract
Interactions between Eph receptor tyrosine kinases (RTKs) and membrane-anch ored ephrin ligands critically regulate axon pathfinding and development of the cardiovascular system, as well as migration of neural cells. Similar t o other RTKs, ligand-activated Eph kinases recruit multiple signalling and adaptor proteins, several of which are involved in growth regulation(1,2). However, in contrast to other RTKs, activation of Eph receptors fails to pr omote cell proliferation(3,4) or to transform rodent fibroblasts(5), indica ting that Eph kinases may initiate signalling pathways that are distinct fr om those transmitted by other RTKs. Here we show that stimulation of endoge nous EphA kinases with ephrin-A1 potently inhibits the Ras/MAPK cascade in a range of cell types, and attenuates activation of mitogen-activated prote in kinase (MAPK) by receptors for platelet-derived growth factor (PDGF), ep idermal growth factor (EGF) and Vascular endothelial growth factor (VEGF). In prostatic epithelial cells and endothelial cells, but not fibroblasts, t reatment with ephrin-A1 inhibits cell proliferation. Our results identify E phA kinases as negative regulators of the Ras/MAPK pathway that exert anti- mitogenic functions in a cell-type-specific manner.