Insulin-like growth factors (IGFs) play an important role in regulating vascular smooth muscle cell (VSMC) proliferation and directed migration. IGFs exert these biological actions through the activation of the @entity2856 and its downstream signaling network. While the involvement of the IRS-PI3 kinase- @entity584 pathway in mediating the chemotactic and mitogenic actions of IGFs is clear, the role of the mitogen-activated protein kinase (MAPK) signaling pathway is still under debate. In this study, the role of @entity1366 in mediating the chemotactic and mitogenic actions of @entity442 in cultured porcine VSMCs was investigated. @entity442 treatment caused a significant increase in the phosphorylation state, as well as the kinase activity, of @entity1366 . Compared to the strong and sustained MAPK activation induced by platelet-derived growth factor-BB, the @entity442 -induced MAPK activation was weaker and more transient. Specific inhibition of the MAPK activation by @entity4286 or @entity5732 , two selective MEK inhibitors, significantly inhibited @entity442 -stimulated cell proliferation, and reduced the number of cells that migrated towards @entity442 . The p38 MAPK inhibitor @entity1441 had no such effect. Likewise, depletion of @entity1366 using antisense oligonucleotides abolished the @entity442 -induced VSMC migration and proliferation. These results suggest that the chemotactic and mitogenic responses of VSMCs to @entity442 require the activation of @entity1366 .

The chemotactic and mitogenic responses of vascular smooth muscle cells to insulin-like growth factor-I require the activation of XXXX .

@entity5732 :: ('MESH:C113580', 'Chemical') :: ['U0126'] @entity442 :: ('3479', 'Gene') :: ['IGF-I'] @entity1441 :: ('MESH:C093642', 'Chemical') :: ['SB203580'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD98059'] @entity2856 :: ('3480', 'Gene') :: ['IGF-I receptor'] @entity1366 :: ('5595;5594', 'Gene') :: ['ERK1/2', 'ERK1 and 2']
@entity1366 :: (5595;5594,Gene) :: ['ERK1/2']
