DLL1 (human), (recombinant)

[Delta-like protein 1, Delta1]



ALX-201-382-C010	10 µg	304.00 USD

ALX-201-382-C050	50 µg	820.00 USD

Product Specification

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.

Shipping:	SHIPPED ON BLUE ICE

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 [1]. 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 [1] is the human homolog of the Drosophila Notch ligand Delta [2]. Sequence analysis predicted that the 723-aa DLL1 transmembrane protein, which is 88% identical to the mouse DLL1 protein [3], 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 [4]. 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 [5]. DLL1 undergoes proteolytic processing in its extracellular domain by ADAM10 and represents a substrate for several other members of the ADAM family [6, 7]. 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 [8-10]. Recently it has been shown that DLL1 is essential for postnatal arteriogenesis [11].

Background / Technical Information:	UniProt link O00548: DLL1 (human) [Precursor] 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.

Please mouse over

General Literature References

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

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

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

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

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

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

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