2007
DOI: 10.1038/sj.onc.1210198
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MKK signaling and vascularization

Abstract: In 1998, George Vande Woude's lab discovered that anthrax lethal factor (LF), the principal virulence component of anthrax toxin, was a zinc-metalloprotease that cleaved and inactivated mitogen-activated protein kinase kinases (MKK). It was perhaps not surprising, given the known roles of MKK1 and 2 in cell proliferation, that LF was subsequently found to dramatically inhibit tumor growth in vivo. What was not anticipated, however, was that the tumors treated with LF would have a substantially reduced vascular… Show more

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Cited by 22 publications
(26 citation statements)
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References 82 publications
(69 reference statements)
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“…ERK1/2 and p38 phosphorylation was reduced in Rap1-depleted endothelial cells. FGF2 signaling through ERK has been shown to play vital roles in endothelial cell functions, including proliferation and vascularization (14), and Rap1 can activate ERK in cell types that express B-Raf (54). ERK phosphorylation in response to FGF2 in HMVECs correlated with Rap1 activation, which occurred within 10 min and was sustained for at least 1 h (Fig.…”
Section: Depletion Of Rap1 In Endothelial Cells Inhibited Tube Formatmentioning
confidence: 96%
See 1 more Smart Citation
“…ERK1/2 and p38 phosphorylation was reduced in Rap1-depleted endothelial cells. FGF2 signaling through ERK has been shown to play vital roles in endothelial cell functions, including proliferation and vascularization (14), and Rap1 can activate ERK in cell types that express B-Raf (54). ERK phosphorylation in response to FGF2 in HMVECs correlated with Rap1 activation, which occurred within 10 min and was sustained for at least 1 h (Fig.…”
Section: Depletion Of Rap1 In Endothelial Cells Inhibited Tube Formatmentioning
confidence: 96%
“…In an attempt to identify other downstream targets of Rap1 in endothelial cells, we examined the phosphorylation of p38, another mitogen-activated protein kinase (MAPK) that is important for endothelial cell migration and angiogenesis (14,24). FGF2 induced a rapid but transient phosphorylation of HMVEC p38 that peaked at 10 min (Fig.…”
Section: Depletion Of Rap1 In Endothelial Cells Inhibited Tube Formatmentioning
confidence: 99%
“…MKK activity regulates vascular endothelial growth factor (VEGF) expression at the transcriptional and posttranscriptional levels (45). The role of ERK activation in angiogenic growth factor signaling has been well established (46).…”
Section: Discussionmentioning
confidence: 99%
“…Activation of the VEGFR2 could recruit kinases such as MAPK, AKT, and Src (50). Endothelial Src and AKT activation have been linked to the regulation of vascular permeability, whereas MEK-MAPK has been more closely associated with proliferation (50)(51)(52)(53)(54). LF could dampen the MEK-MAPK proliferative signal without altering other VEGFR effectors, resulting in increased permeability.…”
Section: Discussionmentioning
confidence: 99%