Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans

Tsai, Ming Tzu; Cheng, Chien Jui; Lin, Yuh‐Charn; Chen, Chun-Chuan; Wu, Ann Ru; Wu, Min Tzu; Hsu, Cheng chin; Yang, Ruey‐Bing

doi:10.1042/bj20090341

Cited by 62 publications

(55 citation statements)

References 40 publications

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“…Based on these data, we suggest that Scube2 CUB domains might also function in morphogenetic patterning and regulated protease recruitment and activation. This is supported by the fact that Scube2 activity is a positive component of the Hh pathway in vivo (Creanga et al, 2012;Tsai et al, 2009). It is known that the loss of Scube2 activity in the zebrafish embryo leads to mild defects in Hh signal transduction (Hollway et al, 2006), and that simultaneous knockdown of all three Scube genes in triple-morpholino embryos phenocopies a complete loss of embryonic Hh function (Johnson et al, 2012).…”

Section: Discussionmentioning

confidence: 57%

“…Importantly, we observed that both Scube activities were CUB-domain-dependent and were strictly linked to proteolytic substrate processing during release. Thus, we suggest that the Scube2 CUB domain (Tsai et al, 2009;Tukachinsky et al, 2012) might prime cell-tethered morphogens for processing, as has been described for the procollagen Cproteinase enhancers PCPE-1 and PCPE-2 (Blanc et al, 2007). PCPEs are CUB-domain-containing extracellular glycoproteins that stimulate the C-terminal processing of fibrillar procollagens (Blanc et al, 2007;Takahara et al, 1994), but which are devoid of intrinsic proteolytic activity.…”

Section: Discussionmentioning

confidence: 95%

“…We hypothesized that the observed difference might stem from the use of amphibian versus mammalian Scube2 in a mammalian expression system, and we tested this idea by coexpressing ShhNp with FLAG-tagged human (h)Scube2 (Tsai et al, 2009). As observed previously for xScube2, hScube2 solubilized nonpalmitoylated ShhNp C25S , and hScube2D (lacking the C-terminal cysteine-rich-and CUB-domain) was less active (Fig.…”

Section: Human Scube2-enhances N-and C-terminal Shhnp Sheddingmentioning

confidence: 99%

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Scube2 enhances proteolytic Shh processing from the surface of Shh-producing cells

Jakobs

Exner

Schürmann

et al. 2014

Journal of Cell Science

112

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All morphogens of the Hedgehog (Hh) family are synthesized as dual-lipidated proteins, which results in their firm attachment to the surface of the cell in which they were produced. Thus, Hh release into the extracellular space requires accessory protein activities. We suggested previously that the proteolytic removal of N-and Cterminal lipidated peptides (shedding) could be one such activity. More recently, the secreted glycoprotein Scube2 (signal peptide, cubulin domain, epidermal-growth-factor-like protein 2) was also implicated in the release of Shh from the cell membrane. This activity strictly depended on the CUB domains of Scube2, which derive their name from the complement serine proteases and from bone morphogenetic protein-1/tolloid metalloproteinases (C1r/C1s, Uegf and Bmp1). CUB domains function as regulators of proteolytic activity in these proteins. This suggested that sheddases and Scube2 might cooperate in Shh release. Here, we confirm that sheddases and Scube2 act cooperatively to increase the pool of soluble bioactive Shh, and that Scube2-dependent morphogen release is unequivocally linked to the proteolytic processing of lipidated Shh termini, resulting in truncated soluble Shh. Thus, Scube2 proteins act as protease enhancers in this setting, revealing newly identified Scube2 functions in Hh signaling regulation.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 95%

Section: Human Scube2-enhances N-and C-terminal Shhnp Sheddingmentioning

confidence: 99%

See 1 more Smart Citation

Scube2 enhances proteolytic Shh processing from the surface of Shh-producing cells

Jakobs

Exner

Schürmann

et al. 2014

Journal of Cell Science

112

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“…The SCUBE family consists of three members: Scube1, Scube2, and Scube3. (Tsai et al 2009;Zhuang et al 2010). SCUBE1 is released in the early period of embryogenesis and is present in platelet alpha granules and endothelial cells .…”

Section: Introductionmentioning

confidence: 99%

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer

Topcu

Kavgacı

Özdemir

et al. 2015

Tohoku J. Exp. Med.

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Breast cancer (BC) is the most common cancer among women and a major cause of death. Signal Peptide-Cub-Epidermal growth factor domain-containing protein-1 (SCUBE1) is secreted under hypoxia and inflammatory conditions from platelet alpha granules. Its biological function is uncertain, although it may be a procoagulant substance in cancer patients. SCUBE1 is useful for identifying thrombotic diseases, including cancers and acute coronary syndromes. D-dimer reflects the relationship between coagulation activation and fibrinolysis; namely, thrombosis and D-dimer levels are closely linked. This is the first investigation of the potential diagnostic and prognostic value of SCUBE1 levels in patients with BC. Fifty patients and 33 age-matched and body mass index-matched healthy controls were enrolled. Blood samples were collected before chemotherapy regimens commenced. Serum SCUBE1 and D-dimer levels were measured before adjuvant chemotherapy and were compared to the healthy controls. SCUBE1 levels were determined using an enzyme-linked immunosorbent assay (ELISA) method. SCUBE1 and D-dimer levels were significantly higher in patients than in the controls (p = 0.03 and p < 0.001, respectively). A cut-off value of 1.55 ng/mL for SCUBE1 was associated with 62% sensitivity and 72.7% specificity and with positive predictive value of 77.5% and negative predictive value of 55.8%. Two patients with high SCUBE1 and D-dimer levels also developed pulmonary embolism. SCUBE1 may indicate hypercoagulability in patients with BC and thus help identify patients at greater risk of thrombosis and requiring anti-thrombosis treatment. SCUBE1 may also be used as an assistant test for identifying patients at risk of BC.

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“…SCUBE1 (signal peptide-CUB-EGF (epidermal growth factor) domain-containing protein 1) is the founding member of the newly identified, secreted, cell membrane-associated SCUBE family (1)(2)(3)(4)(5)(6)(7). This protein family is composed of three distinct members evolutionarily conserved in vertebrates (1, 2, 6 -10).…”

mentioning

confidence: 99%

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

Lee

et al. 2013

Journal of Biological Chemistry

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Background: Roles of zebrafish scube1 in primitive hematopoiesis remain unknown. Results: scube1 knockdown by morpholino-oligonucleotides reduced the expression of marker genes associated with primitive hematopoiesis. Conclusion: scube1 is critical for and acts at the top of the regulatory hierarchy of primitive hematopoiesis by modulating BMP signaling. Significance: Scube1 is a key regulator for primitive hematopoiesis in vertebrates.

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Isolation and characterization of a secreted, cell-surface glycoprotein SCUBE2 from humans

Cited by 62 publications

References 40 publications

Scube2 enhances proteolytic Shh processing from the surface of Shh-producing cells

Scube2 enhances proteolytic Shh processing from the surface of Shh-producing cells

Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with Breast Cancer

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

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