A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCγ1 activation and angiogenesis

Singh, Amrik J.; Meyer, Rosana D.; Navruzbekov, Gyulmagomed; Shelke, Rajani; Duan, Lei; Band, Hamid; Leeman, Susan E.; Rahimi, Nader

doi:10.1073/pnas.0700809104

Cited by 59 publications

(102 citation statements)

References 25 publications

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“…VEGFR2 is internalized upon activation (Gampel et al, 2006;Lanahan et al, 2010), but a portion of the receptor is directed to lysosomes for degradation (Ewan et al, 2006;Singh et al, 2007). The cell surface pool of VEGFR2 is homeostatically replenished by both de novo protein synthesis induced by VEGF signaling itself (Gampel et al, 2006;Domingues et al, 2011) and by recycling of residual intact receptor.…”

Section: Discussionmentioning

confidence: 99%

“…VEGFR2 phosphorylation at Y1175 recruits high-affinity substrates such as PLCc, which activates the MAPK pathway, among others, and Shb, which activates phosphoinositide 3-kinase (PI3K)-Akt pathways (Nagy et al, 2007;Sakurai et al, 2005). Upon internalization post-activation, a portion of the 'spent' VEGFR2 is ubiquitylated and degraded in lysosomes, whereas another portion is recycled to the plasma membrane for another round of activation (Ewan et al, 2006;Singh et al, 2007). In addition, the newly synthesized VEGFR2 is trafficked from the Golgi apparatus to the plasma membrane where it can be activated (Gampel et al, 2006;Manickam et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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KIF13B regulates angiogenesis through golgi-plasma membrane trafficking of VEGFR2

Yamada

Nakajima

Geyer

et al. 2014

Journal of Cell Science

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Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGFmediated endothelial migration, capillary tube formation and neovascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

KIF13B regulates angiogenesis through golgi-plasma membrane trafficking of VEGFR2

Yamada

Nakajima

Geyer

et al. 2014

Journal of Cell Science

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“…The assay was performed as described. 23 Briefly, HEK-293 cells that expressed TMIGD1 were grown in 10-cm plates. The plates were washed with H/S buffer (25 mmol/L HEPES, pH 7.4, 150 mmol/L NaCl, 2 mmol/L Na 3 VO) and lyzed in EB lysis buffer (10 mmol/L Tris-HCl, 10% glycerol, pH 7.4, 5 mmol/L EDTA, 50 mmol/L NaCl, 50 mmol/L NaF, 1% Triton X-100, 1 mmol/L phenylmethylsulfonyl fluoride, 2 mmol/L Na 3 VO 4 , and 20 mg/mL aprotinin).…”

Section: In Vitro Gst Pull-down Assaymentioning

confidence: 99%

TMIGD1 Is a Novel Adhesion Molecule That Protects Epithelial Cells from Oxidative Cell Injury

Arafa

Bondzie

Rezazadeh

et al. 2015

The American Journal of Pathology

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Oxidative damage to renal tubular epithelial cells is a fundamental pathogenic mechanism implicated in both acute kidney injury and chronic kidney diseases. Because epithelial cell survival influences the outcome of acute kidney injury and chronic kidney diseases, identifying its molecular regulators could provide new insight into pathobiology and possible new therapeutic strategies for these diseases. We have identified transmembrane and immunoglobulin domain-containing 1 (TMIGD1) as a novel adhesion molecule, which is highly conserved in humans and other species. TMIGD1 is expressed in renal tubular epithelial cells and promotes cell survival. The extracellular domain of TMIGD1 contains two putative immunoglobulin domains and mediates self-dimerization. Our data suggest that TMIGD1 regulates transepithelial electric resistance and permeability of renal epithelial cells. TMIGD1 controls cell migration, cell morphology, and protects renal epithelial cells from oxidative-and nutrient-deprivationeinduced cell injury. Hydrogen peroxide-induced oxidative cell injury downregulates TMIGD1 expression and targets it for ubiquitination. Moreover, TMIGD1 expression is significantly affected in both acute kidney injury and in deoxy-corticosterone acetate and sodium chloride (deoxy-corticosterone acetate salt)-induced chronic hypertensive kidney disease mouse models. Taken together, we have identified TMIGD1 as a novel cell adhesion molecule expressed in kidney epithelial cells that protects kidney epithelial cells from oxidative cell injury to promote cell survival. (Am J Pathol 2015 http://dx

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“…This phenotype has been previously associated with increased invasive and tumorigenic ability. 29 The decreased invasive phenotype in the absence of PTK6 was further tested using conventional transwell assays, where both MDA-MB-231 and RKO cells had a lower invasive ability in the absence of PTK6 (Fig. 3F; Fig.…”

Section: Hypoxia-induced Ptk6 Promotes Cell Motility and Invasionmentioning

confidence: 99%

HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

Pires

Blokland

Broos

et al. 2014

Cancer Biology & Therapy

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A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCγ1 activation and angiogenesis

Cited by 59 publications

References 25 publications

KIF13B regulates angiogenesis through golgi-plasma membrane trafficking of VEGFR2

KIF13B regulates angiogenesis through golgi-plasma membrane trafficking of VEGFR2

TMIGD1 Is a Novel Adhesion Molecule That Protects Epithelial Cells from Oxidative Cell Injury

HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

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