Zebrafish scube1 (Signal Peptide-CUB (Complement Protein C1r/C1s, Uegf, and Bmp1)-EGF (Epidermal Growth Factor) Domain-containing Protein 1) Is Involved in Primitive Hematopoiesis

Tsao, Ku-Chi; Tu, Cheng Fen; Lee, Shyh-Jye; Yang, Ruey‐Bing

doi:10.1074/jbc.m112.375196

Cited by 19 publications

(15 citation statements)

References 50 publications

(59 reference statements)

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“…Because SCUBE2 can regulate VEGF responses both in vitro and in vivo (Figures 1 and 3) and SCUBE proteins can function as coreceptors for signaling receptor serine/threonine kinases or receptor tyrosine kinases, [13][14][15][16] we examined whether SCUBE2 colocalizes and interacts with VEGFR2 in HUVECs. Confocal microscopy and coimmunoprecipitation experiments indeed revealed that VEGF promotes their colocalization at the plasma membrane and enhances the association of SCUBE2 with VEGFR2, peaking at 10 minutes after VEGF stimulation in HUVECs ( Figure 4A To evaluate whether SCUBE2 could indeed increase VEGF binding to VEGFR2, we first produced a functional AP-VEGF Figure 4C).…”

Section: Scube2 Colocalizes and Interacts With Vegfr2 And Potentiatesmentioning

confidence: 99%

Endothelial SCUBE2 Interacts With VEGFR2 and Regulates VEGF-Induced Angiogenesis

Lin

Chao

Yeh

et al. 2017

ATVB

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Objective— Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis, exerts its proangiogenic action by binding to VEGFR2 (VEGF receptor 2), the activity of which is further modulated by VEGFR2 coreceptors such as neuropilins. However, whether VEGFR2 is regulated by additional coreceptors is not clear. To investigate whether SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), a peripheral membrane protein expressed in vascular endothelial cells (ECs) known to bind other signaling receptors, functions as a VEGFR2 coreceptor and to verify the role of SCUBE2 in the VEGF-induced angiogenesis. Approach and Results— SCUBE2 lentiviral overexpression in human ECs increased and short hairpin RNA knockdown inhibited VEGF-induced EC growth and capillary-like network formation on Matrigel. Like VEGF, endothelial SCUBE2 was upregulated by hypoxia-inducible factor-1α at both mRNA and protein levels. EC-specific Scube2 knockout mice were not defective in vascular development but showed impaired VEGF-induced neovascularization in implanted Matrigel plugs and recovery of blood flow after hind-limb ischemia. Coimmunoprecipitation and ligand-binding assays showed that SCUBE2 forms a complex with VEGF and VEGFR2, thus acting as a coreceptor to facilitate VEGF binding and augment VEGFR2 signal activity. SCUBE2 knockdown or genetic knockout suppressed and its overexpression promoted the VEGF-induced activation of downstream proangiogenic and proliferating signals, including VEGFR2 phosphorylation and mitogen-activated protein kinase or AKT activation. Conclusions— Endothelial SCUBE2 may be a novel coreceptor for VEGFR2 and potentiate VEGF-induced signaling in adult angiogenesis.

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Section: Scube2 Colocalizes and Interacts With Vegfr2 And Potentiatesmentioning

confidence: 99%

Endothelial SCUBE2 Interacts With VEGFR2 and Regulates VEGF-Induced Angiogenesis

Lin

Chao

Yeh

et al. 2017

ATVB

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“…S3C). Interestingly, mRNA expression of Bmp2 and Scube1 (signal peptide-CUB domain EGF-related 1), a potential SHH and BMP signaling regulator (Johnson et al, 2012;Tsao et al, 2013), was expanded in the absence of epidermal NF-κB activity. ISH revealed that Bmp2 and Scube1 were ubiquitously expressed in the epidermis of ΔN embryos at E14.5, whereas expression was restricted to primary HF placodes in controls (Fig.…”

Section: Introductionmentioning

confidence: 99%

LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth

et al. 2016

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In the epidermis of mice lacking transcription factor nuclear factorkappa B (NF-κB) activity, primary hair follicle (HF) pre-placode formation is initiated without progression to proper placodes. NF-κB modulates WNT and SHH signaling at early stages of HF development, but this does not fully account for the phenotypes observed upon NF-κB inhibition. To identify additional NF-κB target genes, we developed a novel method to isolate and transcriptionally profile primary HF placodes with active NF-κB signaling. In parallel, we compared gene expression at the same developmental stage in NF-κB-deficient embryos and controls. This uncovered novel NF-κB target genes with potential roles in priming HF placodes for downgrowth. Importantly, we identify Lhx2 (encoding a LIM/homeobox transcription factor) as a direct NF-κB target gene, loss of which replicates a subset of phenotypes seen in NF-κB-deficient embryos. Lhx2 and Tgfb2 knockout embryos exhibit very similar abnormalities in HF development, including failure of the E-cadherin suppression required for follicle down-growth. We show that TGFβ2 signaling is impaired in NF-κB-deficient and Lhx2 knockout embryos and that exogenous TGFβ2 rescues the HF phenotypes in Lhx2 knockout skin explants, indicating that it operates downstream of LHX2. These findings identify a novel NF-κB/LHX2/TGFβ2 signaling axis that is crucial for primary HF morphogenesis, which may also function more broadly in development and disease.

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“…scube1 and scube2) produced no apparent defect on myod1 expression in the lateral somites (4,12). These observations can be due simply to a distinctive, nonoverlapping spatiotemporal expression pattern and thus nonredundant functions for each scube gene during early zebrafish embryogenesis.…”

Section: Discussionmentioning

confidence: 72%

“…The scube3 tMO1 targets the 5Ј-UTR and scube3 tMO2 blocks the AUG translation start site of zebrafish scube3. The scube3 tMOs diluted in Danieau buffer (12) were injected at the one-or two-cell stage. Increasing doses of each tMO were injected to examine the phenotypic effects.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, these Scube genes may have critical functions during development in these tissue sites, where delicate signaling of morphogens or growth factors are transmitted by cell surface receptors including receptor serine/ threonine kinases and receptor tyrosine kinases (RTKs) 2 (9,10). We and others have recently shown that SCUBE proteins are involved in modulating the signal activity of hedgehog (Hh) (11) or bone morphogenetic protein and TGF-␤ (12)(13)(14), which bind and activate their corresponding G-protein coupled receptors or receptor serine/threonine kinases. However, whether SCUBE proteins can also regulate RTK signaling activity remains unknown.…”

Section: Scube3mentioning

confidence: 99%

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SCUBE3 (Signal Peptide-CUB-EGF Domain-containing Protein 3) Modulates Fibroblast Growth Factor Signaling during Fast Muscle Development

Tu¹,

Tsao²,

Lee³

et al. 2014

Journal of Biological Chemistry

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Background: Function and signaling mediated by SCUBE3 during development remain poorly understood. Results: Loss and gain of function studies showed that SCUBE3 could modulate FGF8 signal activity for fast muscle development. Conclusion: scube3 is critical for and acts at top of the regulatory hierarchy of fast fiber myogenesis by enhancing fgf8 signaling. Significance: Scube3 is a key regulator for fast muscle development in vertebrates.

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Zebrafish scube1 (Signal Peptide-CUB (Complement Protein C1r/C1s, Uegf, and Bmp1)-EGF (Epidermal Growth Factor) Domain-containing Protein 1) Is Involved in Primitive Hematopoiesis

Cited by 19 publications

References 50 publications

Endothelial SCUBE2 Interacts With VEGFR2 and Regulates VEGF-Induced Angiogenesis

Endothelial SCUBE2 Interacts With VEGFR2 and Regulates VEGF-Induced Angiogenesis

LHX2 is a direct NF-κB target gene that promotes primary hair follicle placode down-growth

SCUBE3 (Signal Peptide-CUB-EGF Domain-containing Protein 3) Modulates Fibroblast Growth Factor Signaling during Fast Muscle Development

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