Src family kinases and nitric oxide production are required for hepatocyte growth factor-stimulated endothelial cell growth

Maejima, Yasuhiro; Ueba, Hiroto; Kuroki, Masahide; Yasu, Takanori; Hashimoto, Shingo; Nabata, Aoi; Kobayashi, Nobuhiko; Ikeda, Nahoko; Saito, Muneyasu; Kawakami, Masanobu

doi:10.1016/s0021-9150(02)00384-2

Cited by 23 publications

(19 citation statements)

References 28 publications

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“…Subsequent studies have established that SFKs are involved in signaling from many RTKs, including PDGF receptor (PDGF-R), epidermal growth factor receptor (EGF-R), fibroblast growth factor receptor (FGF-R), insulin-like growth factor-1 receptor (IGF-1R), hepatocyte growth factor/scatter factor receptor (HGF-R), colony-stimulating factor-1 receptor (CSF-1R), stem cell factor receptor (SCF-R), muscle specific kinase (MuSK), and others (Belsches et al, 1997;Parsons and Parsons, 1997;Krystal et al, 1998;Biscardi et al, 1999b;Abram and Courtneidge, 2000;Dey et al, 2000;Hong et al, 2004;Mohamed et al, 2001;Maejima et al, 2003). SFKs can promote mitogenic signaling from growth factor receptors in a number of ways, including initiation of signaling pathways required for DNA synthesis, control of receptor turnover (Ware et al, 1997;Wilde et al, 1999), actin cytoskeleton rearrangements and motility (Chang et al, 1995;Weernink and Rijksen, 1995), and survival (Karni et al, 1999).…”

Section: Sfks Are Downstream Of Several Rtksmentioning

confidence: 99%

“…In these cases, less is known about the mechanism of SFK activation, and how SFKs participate in signaling from each receptor class. We know that activation of the HGF receptor Met results in the association of a number of signaling molecules, including Src, and there is some evidence that HGF stimulated mitogenesis may require SFKs (Weidner et al, 1993;Chen et al, 1998;Maejima et al, 2003). Stimulation of RTKs of the Axl family, including Axl and Sky, also results in SFK activation (Toshima et al, 1995;Braunger et al, 1997).…”

Section: Sfks Promote Rtk-initiated Dna Synthesismentioning

confidence: 99%

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The interplay between Src family kinases and receptor tyrosine kinases

2004

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Src family tyrosine kinases (SFKs) are involved in a diverse array of physiological processes, as highlighted in this review. An overview of how SFKs interact with, and participate in signaling from, receptor tyrosine kinases (RTKs) is discussed. And also, how SFKs are activated by RTKs, and how SFKs, in turn, can activate RTKs, as well as how SFKs can promote signaling from growth factor receptors in a number of ways including participation in signaling pathways required for DNA synthesis, control of receptor turnover, actin cytoskeleton rearrangements and motility, and survival are discussed.

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Section: Sfks Are Downstream Of Several Rtksmentioning

confidence: 99%

Section: Sfks Promote Rtk-initiated Dna Synthesismentioning

confidence: 99%

The interplay between Src family kinases and receptor tyrosine kinases

2004

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“…4C). Srcdependent phosphorylation and/or modulation of p145 met has been documented (Rahimi et al, 1998;Cutrupi et al, 2000;Chan et al, 2003;Maejima et al, 2003;Popsueva et al, 2003;Sridhar et al, 2005), although there was no clear demonstration of the phosphorylation site(s).…”

Section: Discussionmentioning

confidence: 99%

Tyrosine phosphorylation of p145met mediated by EGFR and Src is required for serum-independent survival of human bladder carcinoma cells

Yamamoto

Mammadova

Song

et al. 2006

Journal of Cell Science

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Here we address the molecular mechanism of serum-independent survival and growth of human bladder carcinoma cell line 5637. Serum starvation promoted tyrosine phosphorylation of a 145-kDa protein and activation of the tyrosine kinase Src and the receptor for epidermal growth factor (EGFR) over a slow time course (>8 hours). The phosphorylated 145-kDa protein was identified as the β-subunit of c-Met/hepatocyte growth factor (HGF) receptor, p145met, in which tyrosine residues 1003, 1234, and 1235 were phosphorylated. Inhibitors of Src (PP2, SU6656) or EGFR (AG99), but not p145met (K252a), effectively blocked tyrosine phosphorylation of p145met and promoted cell death accompanied by activation of caspase-like proteases. Conditioned medium from the serum-starved 5637 cells or purified EGF readily promoted the activation of Src and EGFR, and tyrosine phosphorylation of p145met in normally grown 5637 cells, suggesting that autocrine signaling of EGFR ligands is responsible for signal transduction events in serum-starved cells. Consistent with this idea, a monoclonal antibody against EGFR that would interfere with the ligand binding to EGFR blocked tyrosine phosphorylation events and promoted the caspase activation and cell death in serum-free conditions. Such apoptotic cell death was also induced by pretreatment of cells with a high concentration of HGF that downregulated endogenous p145met. Nevertheless, Cu2+ ions, competitive inhibitors for HGF-binding to p145met, did not show any effect on cellular functions in serum-free conditions. These results suggest that the serum-independent growth of 5637 cells involves the transmembrane signaling cascade via EGFR ligand(s) (but not HGF), EGFR, Src and p145met.

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“…We previously reported that HGF promotes vascular endothelial growth via an endogenous nitric oxide (NO)-dependent pathway, 24 and Böger et al demonstrated that administration of L-arginine, a precursor of NO, improves the symptoms of ASO patients. 25 Increased shear stress as a result of exercise activates endothelial NO synthase and thus, NO may play an important role in heparin -exercise therapy in patients with ASO.…”

Section: Discussionmentioning

confidence: 99%

Exercise After Heparin Administration

Maejima

Yasu

Ueba

et al. 2005

Circ J

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he number of patients with arteriosclerosis obliterans (ASO), an atherosclerotic peripheral arterial occlusive disease, is estimated at 500-1,000 individuals per million per year, 1 and the prevalence of intermittent claudication was higher than 1% in a free-living, elderly, North American population. 2 Although bypass operation, stenting and atherectomy are effective therapies for patients with stenosis in the proximal large arteries such as the iliac arteries or femoral arteries, their effects are limited in ASO patients in whom stenotic lesions extend to peripheral small arteries (poor run-off). Enhancement of collateral vessel formation and angiogenesis is a promising therapeutic modality for such non-option ASO patients. Heparin administration reportedly improves the symptoms of ASO Circulation Journal Vol.69, September 2005 patients 9 months after the treatment, 3 and increases the exercise capacity of severe coronary heart disease (CHD) patients by enhancing collateral vessel growth. 4 Recently, investigators have shown that systemic administration of heparin increases the concentration of plasma hepatocyte growth factor (HGF), which promotes neovascularization, [5][6][7] and other studies have shown the effectiveness in ASO and CHD patients of therapeutic angiogenesis using certain growth factors. 8,9 The mechanism of the therapeutic effect of heparin in ASO patients may be strongly related to HGF. There have been no previous studies of whether the combination of an exercise program and heparin administration additionally improves the symptoms of ASO.The aim of the present study was to determine whether a program combining heparin administration with exercise is a useful therapeutic strategy for stimulation of development of collateral circulation in the ischemic legs of patients with non-option ASO. Methods Study PatientsAll subjects had severe chronic limb ischemia that lead to claudication within 400 m of walking. None of the subjects was a candidate for non-surgical or surgical revascularization because of the lack of distal target vessels or for other reasons, such as comorbidities that would increase Background A prospective study examined whether a combination of an exercise program and heparin administration improves the clinical symptoms of patients with arteriosclerosis obliterans (ASO) without an indication for surgical revascularization because of the lack of distal target vessels or other reasons such as high surgical risk or lack of a vein conduit from previous coronary artery bypass surgery. Methods and Results A total of 19 consecutive patients with symptomatic non-option ASO diagnosed by angiography were randomly assigned to 3 groups: heparin + exercise (walking for 60 min after heparin injection [3,000 units/day IV for 14 days], n=6), heparin administration only (n=6), and exercise only (n=7). Plasma levels of hepatocyte growth factor (HGF) were serially measured before and after intravenous administration of heparin. Ankle brachial pressure index was measured and treadmill exercise ...

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Src family kinases and nitric oxide production are required for hepatocyte growth factor-stimulated endothelial cell growth

Cited by 23 publications

References 28 publications

The interplay between Src family kinases and receptor tyrosine kinases

The interplay between Src family kinases and receptor tyrosine kinases

Tyrosine phosphorylation of p145met mediated by EGFR and Src is required for serum-independent survival of human bladder carcinoma cells

Exercise After Heparin Administration

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