The JNK (c-Jun NH2-terminal kinase) signal transduction cascade is one of three identified MAP kinase pathways in mammals.
JNK pathway activation occurs in response to environmental stress, is associated with the nuclear accumulation of JNK itself, and is implicated in the immune response, cellular proliferation, oncogenic transformation, morphogenesis, and apoptosis.
JIP1 (JNK-interacting protein-1, also known as Islet Brain-1 and mitogen-activated protein kinase 8-interacting protein-1,) is a cytoplasmic protein that possesses an N-terminal JNK-binding domain and a C-terminal SRC homology (SH3) domain.
Its SH3 domain is related to the SH3 domains of the tyrosine kinase c-Fyn and the p85 subunit of phosphoinositide-3 kinase (PI3K).
Overexpression of JIP1 causes cytoplasmic retention of JNK, thereby preventing its nuclear accumulation and the subsequent activation of the JNK pathway.
This observation led to the original hypothesis that JIP1 acts as a cytoplasmic anchor for JNK.
JIP1 has been shown to bind selectively to JNK but not to the ERK or p38 MAP kinases; it has also demonstrated selectivity in its binding to specific proteins of the JNK pathway.
In addition to JNK, JIP1 binds to the JNK activator MKK7 (MAP kinase kinase 7) and the MKK7 activators MLK3 (mixed-lineage protein kinase 3) and DLK (dual leucine zipper-bearing kinase), all at separate binding sites.
JIP1’s assembly of multiple components of the JNK pathway into a functional signaling module provides precise regulation of the JNK cascade and defines JIP1 as a JNK-scaffolding protein.
Multiple transcription variants of JIP1 have been cloned: JIP1 has been identified in brain and kidney tissues while JIP2a, JIP2b, and JIP3 are specifically expressed in the brain, particularly in the adult cerebral cortex and hippocampus.
All JIP1 isoforms inhibit JNK signaling when overexpressed.
A recent study has discovered a direct interaction between JIP1 and amyloid-b-precursor protein (APP), the precursor to the b-amyloid peptide that comprises the amyloid plaques characteristic of Alzheimer’s disease, in the adult mouse brain.
Taken together with previous reports of active JNK in the brains of Alzheimer’s disease patients, this evidence suggests that the JNK signaling pathway, and thus the scaffolding function of JIP1, may be fundamental to the progression of Alzheimer’s disease.
Applications:Suitable for use in Western Blot and Immunoprecipitation.
Other applications have not been tested.
Recommended Dilutions:Optimal dilutions to be determined by the researcher.
Storage and Stability:May be stored at 4°C for short-term only.
Aliquot to avoid repeated freezing and thawing.
Store at -20°C.
Aliquots are stable for 12 months after receipt.
For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
仕様
Size：100ug
Host：rabbit
Source Antibody：human
Grade：Affinity Purified
Purity：Purified by immunoaffinity chromatography.
Form：Supplied as liquid in PBS, pH 7.4, 0.09% sodium azide.
Specificity：Recognizes human JIP1. Species Crossreactivity: mouse
Isotype：IgG
Calc Applications Abbrev：IP WB
Calc Crossreactivity：Hu Mo
Immunogen：Synthetic peptide derived from the N-terminal region of the human JIP1 protein.
