Protein kinase C decreases the hepatocyte growth factor-induced activation of Erk1/Erk2 MAP kinases

Sipeki, Szabolcs; Bander, Erzsébet; Farkas, Gyöngyi; Gujdár, Annamária; Ways, D. Kirk; Farago, Anna F.

doi:10.1016/s0898-6568(00)00105-4

Cited by 12 publications

(7 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, it has been reported that MEK1/2 inhibition can diminish HGF/SF-induced Akt phosphorylation, as a substrate of PI 3-kinase (Delehedde et al, 2001;Yu et al, 2001), or vice versa. PI 3-kinase inhibition may also block HGF/SF-induced ERK1/2 activation, as a substrate of MEK1/2 (Delehedde et al, 2001;Sipeki et al, 2000). In our studies, however, neither MEK1/2 inhibition blocked Akt phosphorylation nor PI 3-kinase inhibition reduced ERK1/2 activation (Fig.…”

Section: Hgf/sf-induced Vegf/vpf Gene Expression Is Mediated Via Acticontrasting

confidence: 51%

Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription

Reisinger

Kaufmann

Gille

2003

Journal of Cell Science

View full text Add to dashboard Cite

Hepatocyte growth factor (HGF/SF)-induced expression of vascular endothelial growth factor (VEGF/VPF) has been implicated in paracrine amplification of angiogenesis, contributing to angiogenic responses during inflammation, wound healing, collateral formation and tumor growth. We have shown previously that HGF/SF-mediated VEGF/VPF expression by keratinocytes is primarily dependent on transcriptional activation, and we mapped the HGF/SF-responsive element to a GC-rich region between bp -88 and -65. Sp1-like factors bind to this element constitutively; however the VEGF/VPF promoter is transactivated by HGF/SF in the absence of induced binding activity. In experimental approaches to clarify molecular mechanisms of Sp1-dependent VEGF/VPF gene transcription, neither HGF/SF-dependent changes in nuclear expression nor in relative DNA binding activity of Sp family members to the indicated element were observed. Thus, HGF/SF was hypothesized to induce VEGF/VPF gene transcription via increased transactivation activity of Sp1 owing to biochemical modification. In immunoprecipitation studies, HGF/SF was found to increase the amount of serine-phosphorylated Sp1, revealing a likely mechanism of HGF/SF-induced VEGF/VPF expression, as phosphorylation may enhance the transcriptional activity of Sp1. The contribution of different signaling molecules to HGF/SF-induced VEGF/VPF transcription was demonstrated by the use of chemical inhibition, of expression of kinase-deficient signaling proteins, and by the use of antisense oligonucleotides. Herein, we provide evidence that PI 3-kinase, MEK1/2 and PKC-ζ play a significant role in HGF/SF-induced VEGF/VPF promoter activation. Together, our results elucidate a critical pathway of paracrine amplification of angiogenesis, suggesting that HGF/SF-induced Sp1 phosphorylation may activate VEGF/VPF promoter activity that requires the contribution of distinct signaling molecules.

show abstract

Section: Hgf/sf-induced Vegf/vpf Gene Expression Is Mediated Via Acticontrasting

confidence: 51%

Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription

Reisinger

Kaufmann

Gille

2003

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…The negative regulatory effect of PKC on ERK/JNK cascade has been demonstrated in our and other's reports [32,39,55]. Kermorgant et al suggested that PKCε-mediated ERK suppression was achieved by facilitating the dissociation of ERK from c-Met-MEK endosomal signaling cascade to focal complexes [40], however, the underlying mechanisms were not fully clarified.…”

Section: Discussionmentioning

confidence: 67%

PKCε-mediated c-Met endosomal processing directs fluctuant c-Met-JNK-paxillin signaling for tumor progression of HepG2

Cheng

et al. 2015

Cellular Signalling

View full text Add to dashboard Cite

“…Endosome to a Perinuclear Compartment-It has been shown that PKC can negatively influence c-Met signaling (21,23). To establish whether this action is effected through the control of HGFinduced traffic of c-Met, an inhibitor of PKC, BIM-I (bisindolylmaleimide I) was employed.…”

Section: Pkc Controls the Movement Of C-met From Earlymentioning

confidence: 99%

“…For example this is the case for the ␥-aminobutyric type A receptor, the parathyroid hormone receptor 1, and the sst2A somatostatin receptor (18 -20). Prior evidence indicates that PKC plays a negative role in controlling c-Met function (21), however it is not known how this relates to the internalization or traffic of c-Met.…”

mentioning

confidence: 99%

Protein Kinase C Controls Microtubule-based Traffic but Not Proteasomal Degradation of c-Met

Kermorgant

Zicha

Parker

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Protein kinase C decreases the hepatocyte growth factor-induced activation of Erk1/Erk2 MAP kinases

Cited by 12 publications

References 21 publications

Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription

Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription

PKCε-mediated c-Met endosomal processing directs fluctuant c-Met-JNK-paxillin signaling for tumor progression of HepG2

Protein Kinase C Controls Microtubule-based Traffic but Not Proteasomal Degradation of c-Met

Contact Info

Product

Resources

About