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Notch Signaling

The highly-conserved Notch signaling pathway is unique, as both the Notch receptor and most of its respective ligands (canonically the DSL or Delta/Serrate/lag-2 family members) are transmembrane proteins attached to the cell surface. Therefore, Notch signaling is limited to interaction between adjacent cells.

Communication between adjacent cells is paramount, particularly during early development, when cell fate and function are yet to be determined. Notch signaling provides a method for cells to specify their own identity, and to simultaneously influence the role and identity of neighboring cells through lateral inhibition.

The core of the Notch signaling pathway involves two adjacent cells, one expressing a DSL family ligand, and the other expressing the Notch (the receptor). When receptor and ligand interact, two separate protease enzymes cleave Notch into extracellular and cytosolic components. ADAM proteases cleave the extracellular portion of Notch, which remains bound to its respective ligand and is endocytosed by the signaling cell. γ-secretase cleaves the cytosolic portion of notch. This cytosolic region migrates to the nucleus where it binds to the transcription factor CSL, transforming it from a transcriptional repressor to an activator, and upregulating expression of Notch target genes.

Notch

NOTCH1 - Notch1

This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling...   More...

Notch Antagonists

AP2A1 (Adaptor-Related Protein Complex 2, alpha 1 Subunit):

This gene encodes the alpha 1 adaptin subunit of the adaptor protein 2 (AP-2) complex found in clathrin coated vesicles. The AP-2 complex is a heterotetramer consisting of two large adaptins (alpha or beta), a medium adaptin (mu), and a small adaptin (sigma). The complex is part of the protein coat on the cytoplasmic face of coated vesicles which links clathrin to receptors in vesicles....   More...

NEDD4 (Neural Precursor Cell Expressed, Developmentally Down-Regulated 4, E3 Ubiquitin Protein Ligase):

Notch Ligands

DLL1 (delta-Like 1):

DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication. [provided by RefSeq, Jul 2008].   More...

SRRT (Serrate RNA Effector Molecule Homolog (Arabidopsis)):

Notch Processing

FURIN (Furin (Paired Basic Amino Acid Cleaving Enzyme)):

The protein encoded by this gene belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein is a calcium-dependent serine endoprotease that can efficiently cleave precursor proteins at their paired basic amino acid processing sites. Some of...   More...

LFNG (LFNG O-Fucosylpeptide 3-beta-N-Acetylglucosaminyltransferase):

RFNG (RFNG O-Fucosylpeptide 3-beta-N-Acetylglucosaminyltransferase):

Notch Directed Proteases

ADAM10 (ADAM Metallopeptidase Domain 10):

Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. [provided by RefSeq, Jul 2008].   More...

APH1A (Anterior Pharynx Defective 1 Homolog A (C. Elegans)):

Pathway Agonists

CRB1 (Crumbs Homolog 1 (Drosophila)):

This gene encodes a protein which is similar to the Drosophila crumbs protein and localizes to the inner segment of mammalian photoreceptors. In Drosophila crumbs localizes to the stalk of the fly photoreceptor and may be a component of the molecular scaffold that controls proper development of polarity in the eye. Mutations in this gene are associated with a severe form of retinitis...   More...

NEURL1B (Neuralized Homolog 1B (Drosophila)):

NEURL (Neuralized Homolog (Drosophila)):

Transcription Factors

KCNJ5 (Potassium Inwardly-Rectifying Channel, Subfamily J, Member 5):

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins. It may associate with...   More...

RBPJ (Recombination Signal Binding Protein For Immunoglobulin kappa J Region):

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