Delta-like protein 4
(DLL4) is a type I membrane protein belonging to the Delta/Serrate/Lag2 (DSL)
family of Notch ligands. Notch signaling is an evolutionarily conserved pathway
that controls cell fate and is required in multiple developmental processes
including vascular development, hematopoiesis, somatogenesis, myogenesis, and
neurogenesis. Activates NOTCH1 and NOTCH4. Interactions of Notch receptors with
their ligands result in reciprocal regulated intramembrane proteolysis (RIP).
RIP is a mechanism for transmembrane signal transduction that involves the
sequential processing by a disintegrin metalloprotease (ADAM) and then by
presenilin/ gamma secretase, resulting in shedding of the extracellular domains
and the generation of the soluble ICD signaling fragments, respectively.The
Notch ICD translocates to the nucleus and interacts with transcriptional
coactivators, resulting in the transcription of target genes. The ICDs of the
Notch ligands have also been shown to translocate to the nucleus where they may
have a signaling function. Involved in angiogenesis; Negatively regulates
endothelial cell proliferation and migration and angiogenic sprouting.Essential
for retinal progenitor proliferation.Required for suppressing rod fates in late
retinal progenitors as well as for proper generation of other retinal cell
types. During spinal cord neurogenesis, inhibits V2a interneuron fate.
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