DLL4

Delta-like 4 (Drosophila)

Identifiers

DLL4 ; hdelta2

External IDs

OMIM: 605185 MGI: 1859388 HomoloGene: 10411 GeneCards: DLL4 Gene

Gene ontology
Molecular function	• Notch binding • calcium ion binding
Cellular component	• plasma membrane • integral component of membrane
Biological process	• negative regulation of transcription from RNA polymerase II promoter • angiogenesis • patterning of blood vessels • blood vessel remodeling • cardiac ventricle morphogenesis • cardiac atrium morphogenesis • ventricular trabecula myocardium morphogenesis • pericardium morphogenesis • signal transduction • Notch signaling pathway • Notch receptor processing • visual perception • blood circulation • negative regulation of cell proliferation • negative regulation of endothelial cell migration • dorsal aorta morphogenesis • cellular response to vascular endothelial growth factor stimulus • cellular response to fibroblast growth factor stimulus • regulation of neurogenesis • ventral spinal cord interneuron fate commitment • regulation of neural retina development • Notch signaling involved in heart development • blood vessel lumenization • negative regulation of cell migration involved in sprouting angiogenesis • positive regulation of neural precursor cell proliferation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 15:
41.22 – 41.23 Mb

Chr 2:
119.33 – 119.34 Mb

PubMed search

Delta like ligand 4 is a protein that in humans is encoded by the DLL4 gene.^[1]^[2]

This gene is a homolog of the Drosophila delta gene. The delta gene family encodes Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain.^[2]

References

↑ Shutter JR, Scully S, Fan W, Richards WG, Kitajewski J, Deblandre GA, Kintner CR, Stark KL (Jul 2000). "Dll4, a novel Notch ligand expressed in arterial endothelium". Genes Dev 14 (11): 1313–8. PMC 316657. PMID 10837024.
↑ 2.0 2.1 "Entrez Gene: DLL4 delta-like 4 (Drosophila)".

Yoneya T, Tahara T, Nagao K et al. (2001). "Molecular cloning of delta-4, a new mouse and human Notch ligand.". J. Biochem. 129 (1): 27–34. doi:10.1093/oxfordjournals.jbchem.a002832. PMID 11134954.
Yan XQ, Sarmiento U, Sun Y et al. (2002). "A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer.". Blood 98 (13): 3793–9. doi:10.1182/blood.V98.13.3793. PMID 11739188.
Mailhos C, Modlich U, Lewis J et al. (2002). "Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis.". Differentiation 69 (2–3): 135–44. doi:10.1046/j.1432-0436.2001.690207.x. PMID 11798067.
Dorsch M, Zheng G, Yowe D et al. (2002). "Ectopic expression of Delta4 impairs hematopoietic development and leads to lymphoproliferative disease". Blood 100 (6): 2046–55. PMID 12200365.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Liu ZJ, Shirakawa T, Li Y et al. (2003). "Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis". Mol. Cell. Biol. 23 (1): 14–25. doi:10.1128/MCB.23.1.14-25.2003. PMC 140667. PMID 12482957.
Tohda S, Murata-Ohsawa M, Sakano S, Nara N (2003). "Notch ligands, Delta-1 and Delta-4 suppress the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines". Int. J. Oncol. 22 (5): 1073–9. doi:10.3892/ijo.22.5.1073. PMID 12684674.
Shawber CJ, Das I, Francisco E, Kitajewski J (2003). "Notch signaling in primary endothelial cells". Ann. N. Y. Acad. Sci. 995: 162–70. doi:10.1111/j.1749-6632.2003.tb03219.x. PMID 12814948.
Clark HF, Gurney AL, Abaya E et al. (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
Lauret E, Catelain C, Titeux M et al. (2004). "Membrane-bound delta-4 notch ligand reduces the proliferative activity of primitive human hematopoietic CD34+CD38low cells while maintaining their LTC-IC potential". Leukemia 18 (4): 788–97. doi:10.1038/sj.leu.2403288. PMID 14990974.
Zhang Z, Henzel WJ (2005). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Sci. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
McKeane DP, Meyer J, Dobrin SE et al. (2005). "No causative DLL4 mutations in periodic catatonia patients from 15q15 linked families". Schizophrenia Research 75 (1): 1–3. doi:10.1016/j.schres.2004.07.017. PMID 15820317.
Patel NS, Li JL, Generali D et al. (2005). "Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function". Cancer Res. 65 (19): 8690–7. doi:10.1158/0008-5472.CAN-05-1208. PMID 16204037.
Patel NS, Dobbie MS, Rochester M et al. (2006). "Up-regulation of endothelial delta-like 4 expression correlates with vessel maturation in bladder cancer". Clin. Cancer Res. 12 (16): 4836–44. doi:10.1158/1078-0432.CCR-06-0285. PMID 16914569.
Lefort N, Benne C, Lelièvre JD et al. (2007). "Short exposure to Notch ligand Delta-4 is sufficient to induce T-cell differentiation program and to increase the T cell potential of primary human CD34+ cells". Exp. Hematol. 34 (12): 1720–9. doi:10.1016/j.exphem.2006.08.007. PMID 17157169.
Fung E, Tang SM, Canner JP et al. (2007). "Delta-like 4 induces notch signaling in macrophages: implications for inflammation". Circulation 115 (23): 2948–56. doi:10.1161/CIRCULATIONAHA.106.675462. PMID 17533181.
Hodkinson PS, Elliott PA, Lad Y et al. (2007). "Mammalian NOTCH-1 activates beta1 integrins via the small GTPase R-Ras". J. Biol. Chem. 282 (39): 28991–9001. doi:10.1074/jbc.M703601200. PMID 17664272.
Zang S, Ji Ch, Qu X et al. (2007). "A study on Notch signaling in human breast cancer". Neoplasma 54 (4): 304–10. PMID 17822320.

Signaling pathway: notch signaling pathway

Receptor on signaling cell

Delta: DLL1; DLL3; DLL4

Ligand

Jagged: JAG1; JAG2

Receptor on receiving cell

Notch-1
Notch-2
NOTCH3
NOTCH4

Index of signal transduction

Description	Intercellular neuropeptides growth factors cytokines hormones Cell surface receptors ligand-gated enzyme-linked G protein-coupled immunoglobulin superfamily integrins neuropeptide growth factor cytokine Intracellular adaptor proteins GTP-binding MAP kinase Calcium signaling Lipid signaling Pathways hedgehog Wnt TGF beta MAPK ERK notch JAK-STAT apoptosis hippo TLR

DLL4

References

Further reading