DLL1 (human), (recombinant)

Notch ligand



ALX-201-382-C010	10 µg	185.00 USD

ALX-201-382-C050	50 µg	365.00 USD

Product Specification

Alternative Name:	Delta-like protein 1, Delta1

Concentration:	~0.3mg/ml

Endotoxin Content:	<0.1EU/µg protein (LAL-test).

Purity:	≥90% (SDS-PAGE)

Formulation:	Liquid. 0.2µm-filtered solution in PBS.

Biological Activity:	Inhibits adipogenesis of mesenchymal stem cells.

Source/Host:	Produced in HEK 293 cells. Signal peptide and extracellular domain of recombinant human DLL1 (Delta-like protein 1; Delta1) (aa 1-545) are fused at the C-terminus to a FLAG^®-tag.

Long Term Storage:	-20°C

Use/Stability:	Working aliquots are stable for up to 3 months when stored at -20°C.

Handling:	After opening, prepare aliquots and store at -20°C. Avoid freeze/thaw cycles.

Miscellaneous/General:	Notch signalling pathways play key roles in cell-fate determination and differentiation in many tissues during embryonic and postnatal development. Notch ligands are divided into two subclasses, the delta and the serrate family. Delta-like 1, 3, and 4 (DLL1, -3, -4), JAG1 and JAG2 with DSL (Delta, Serrate, Lag2) domain are typical Notch ligands, while DNER, F3/Contactin and NB-3 without DSL domain are atypical Notch ligands. Notch-ligand binding to NOTCH1, -2, -3, or -4 receptor induces the receptor proteolysis by metalloprotease and γ-secretase to release Notch intracellular domain (NICD). DLL1 is the human homolog of the Drosophila Notch ligand Delta. Sequence analysis predicted that the 723-aa DLL1 transmembrane protein, which is 88% identical to the mouse DLL1 protein, has a DSL domain followed by 8 tandem EGF-like repeats and a short cytoplasmic C-terminal region. A soluble fusion protein containing the DSL domain of DLL1 and its adjacent 50 N-terminal aa inhibited the differentiation of myeloid progenitors but promoted their expansion. DLL1 blocks the differentiation of progenitor cells into the B cell lineage while promoting the emergence of a population of cells with the characteristics of a T cell/NK cell precursor. DLL1 undergoes proteolytic processing in its extracellular domain by ADAM10 and represents a substrate for several other members of the ADAM family. The soluble 38kDa Delta1 intracellular domain (DICD) that is generated by the presenilin-dependent γ-secretase cleavage is transported into the nucleus and likely plays a role in transcriptional events. It has been shown that DLL1 is essential for postnatal arteriogenesis.

Background / Technical Information:	UniProt ID O00548: DLL1 (human) FLAG is a registered trademark of Sigma-Aldrich Co.

Figure 1: SDS-PAGE of DLL1 (human) (recombinant) (Prod. No. ALX-201-382).

Figure 2: Differentiation of human mesenchymal stem cells (MSCs) into adipocytes in the presence or absence of Notch ligands that inhibit adipogenic differentiation of MSCs. Method: MSCs were maintained in DMEM, supplemented with 10% fetal bovine serum, penicilin-streptomycin and glutamine. For differentiation of MSCs they were cultured in adipogenic medium corresponding to growth medium supplemented with 1μM dexamethasone, 0.5mM IBMX, 10μg/m insulin, 100μM indomethacin (day 1). Medium was changed every 3 days. Staining with Oil Red O was typically performed on day 30. For negative controls, TNF-α (20ng/ml) was added. To immobilize Notch ligands on the plastic surface of the culture plates, plates were first incubated with a solution of anti-FLAG^®antibody (5µg/ml) in PBS for 30 min. at 37°C. Plates coated with antibody were blocked with growth medium for at least 30 min. The plates were incubated with solution of DLL1 (human) (rec.) (Prod. No. ALX-201-382) (5µg/ml) or CD137L, Soluble (mouse) (rec.) (Prod. No. ALX-201-321) (5µg/ml) in growth medium for 2 hours at 37°C. These plates were then used to differentiate MSCs.

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General Literature References

Notch signaling in gastrointestinal tract: M. Katoh; Int. J. Oncol. 30, 247 (2007), Review, Abstract;

Proteolytic processing of delta-like 1 by ADAM proteases: E. Dyczynska, et al.; J. Biol. Chem. 282, 436 (2007), Abstract; Full Text

The Notch Ligand Delta-Like 1 is Essential for Postnatal Arteriogenesis: A. Limbourg, et al.; Circ. Res. 100, 363 (2007), Abstract;

NOTCH signaling as a novel cancer therapeutic target: L. Miele, et al.; Curr. Cancer Drug Targets 6, 313 (2006), Abstract;

Notch-induced proteolysis and nuclear localization of the Delta ligand: C.E. Bland, et al.; J. Biol. Chem. 278, 13607 (2003), Abstract; Full Text

The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase: E. Six, et al.; PNAS 100, 7638 (2003), Abstract; Full Text

The Notch ligands, Delta1 and Jagged2, are substrates for presenilin-dependent "gamma-secretase" cleavage: T. Ikeuchi and S.S. Sisodia; J. Biol. Chem. 278, 7751 (2003), Abstract; Full Text

The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments: M.J. LaVoie and D.J. Selkoe; J. Biol. Chem. 278, 34427 (2003), Abstract; Full Text

Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation: A.C. Jaleco, et al.; J. Exp. Med. 194, 991 (2001), Abstract; Full Text

A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells: W. Han, et al.; Blood 95, 1616 (2000), Abstract; Full Text

Human ligands of the Notch receptor: G.E. Gray, et al.; Am. J. Pathol. 154, 785 (1999), Abstract; Full Text

Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta: B. Bettenhausen, et al.; Development 121, 2407 (1995), Abstract; Full Text

The molecular genetics of early neurogenesis in Drosophila melanogaster: E. Knust and J.A. Campos-Ortega; Bioessays 11, 95 (1989), Abstract;