also known as PEBP, for phosphatidylethanolamine-binding protein) is an endogenous inhibitor of the Raf- MAPK kinase (MEK)-MAP kinase pathway. (bmj.com)
Raf kinase inhibitor protein (RKIP) is a member of the phosphatidylethanolamine-binding protein (PEBP) family that interacts with a number of different proteins and regulates multiple signaling pathways. (axonmedchem.com)
PEBP was identified as a physiologically relevant inhibitor of Raf-MEK-ERK and renamed RKIP. (axonmedchem.com)
Plant PEBP proteins play an important role in regulating flowering time, plant architecture as well as seed dormancy. (biomedcentral.com)
Structural analysis revealed highly conserved gene structure and protein motifs among Rosaceae PEBP proteins. (biomedcentral.com)
Carboxypeptidase Y (CPY) inhibitor, IC, shows no homology to any other known proteinase inhibitors and rather belongs to the phosphatidylethanolamine-binding protein (PEBP) family. (nih.gov)
PEBP12
Phosphatidylethanolamine-binding protein 1 is a protein that in humans is encoded by the PEBP1 gene. (wikipedia.org)
Using this strategy we identified catabolic fragments of complement factors, EMILIN2, Von Willebrand factor and phosphatidylethanolamine-binding protein 1 (PEBP1 or RKIP) in patient sera. (nih.gov)
HCNP1
The encoded protein can be further processed to form a smaller cleavage product, hippocampal cholinergic neurostimulating peptide (HCNP), which may be involved in neural development. (nih.gov)
Inhibitory5
Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor ?B signaling that represses tumor invasion and metastasis. (aston.ac.uk)
Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3ß by phosphorylating it at the inhibitory T390 residue. (aston.ac.uk)
CR2 contains important inhibitory phosphorylation sites participating in the negative regulation of Ras binding and Raf activation. (axonmedchem.com)
The structure of the complex contains two binding sites of IC toward CPY, the N-terminal inhibitory reactive site (the primary CPY-binding site) and the secondary CPY-binding site, which interact with the S1 substrate-binding site of CPY and the hydrophobic surface flanked by the active site of the enzyme, respectively. (nih.gov)
The complex structure and analyses of IC mutants for inhibitory activity and the binding to CPY demonstrate that the N-terminal inhibitory reactive site is essential both for inhibitory function and the complex formation with CPY and that the binding of IC to CPY constitutes a novel mode of the proteinase-protein inhibitor interaction. (nih.gov)
Multiple signalin1
From NCBI Gene: This gene encodes a member of the phosphatidylethanolamine-binding family of proteins and has been shown to modulate multiple signaling pathways, including the MAP kinase (MAPK), NF-kappa B, and glycogen synthase kinase-3 (GSK-3) signaling pathways. (nih.gov)
Colorectal cancer4
This study aims at correlating RKIP expression with chromosomal instability in colorectal cancer samples and identifies possible mechanisms of RKIP loss. (bmj.com)
RKIP loss by hypermethylation of its promoter could have a significant influence on colorectal cancer aneuploidy, which might explain its association with metastatic progression. (bmj.com)
RKIP levels in human colorectal cancer positively correlate with GSK3ß expression. (aston.ac.uk)
The aim of this study was to determine the prognostic significance of RKIP expression in colorectal cancer (CRC). (medscape.com)
Mitogen activa2
Raf-1 kinase inhibitor protein (RKIP) is known as a critical down-regulator of the mitogen-activated protein kinase signaling pathway and a potential molecular determinant of malignant metastasis. (medscape.com)
Originally, RKIP was identified as a phospholipid-binding protein and, subsequently, as an interacting partner of Raf-1 kinase that blocks mitogen-activated protein kinase (MAPK) initiated by Raf-1. (medscape.com)
Kinase activity2
Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP" (PDF). (wikipedia.org)
RKIP inhibits the kinase activity of Raf-1 by dissociating the Raf-1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation. (axonmedchem.com)
Inversely2
We demonstrate for the first time that in microsatellite stable (MSS) CRC, the number of chromosomal losses is inversely proportional to RKIP expression levels. (bmj.com)
[ 12 ] A link between RKIP and cancer was first established in prostate cancer, with RKIP showing reduced expression in prostate cancer cells and the lowest expression levels in metastatic cells, suggesting that RKIP expression is inversely associated with the invasiveness of prostate cancer. (medscape.com)
Methylation3
Methyl-specific PCR was used on DNA extracted from 82 cases with CRC to determine CpG methylation status at the RKIP promoter and the results correlated with RKIP protein expression. (bmj.com)
We also show that methylation of the RKIP promoter is a major mechanism by which RKIP expression is silenced in CRC. (bmj.com)
Methylation analysis of 28 cases showed that loss of RKIP expression is unlikely to be due to promoter methylation. (medscape.com)
Highly conserved1
Raf-1 kinase inhibitor protein (RKIP) is a ubiquitously expressed and highly conserved protein that belongs to the phosphatidylethanolamine-binding protein family. (medscape.com)
Phosphorylation1
[ 8 ] Recently, RKIP was shown to inhibit activation of Raf-1 by blocking phosphorylation of Raf-1 by p21-activated kinase and Src family kinases. (medscape.com)
Gene2
Phosphatidylethanolamine-binding proteins (PEBPs) constitute a common gene family found among animals, plants and microbes. (biomedcentral.com)
Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
Membrane3
They are bona fide Ras (a membrane-associated guanine nucleotide-binding protein) effectors and upstream activators of the ubiquitous ERK pathway , which has drawn the attention to these proteins as potential targets in cancer therapy . (axonmedchem.com)
CR1 contains a Ras-binding domain (RBD), which is necessary for the interaction with Ras and with membrane phospholipids required for membrane recruitment, and a cysteine-rich domain (CRD), which is a secondary Ras-binding site and also necessary for the interaction of CR1 with the kinase domain for Raf auto-inhibition. (axonmedchem.com)
The common and key step in the activation of all 3 Raf isoforms is membrane recruitment by a Ras family protein. (axonmedchem.com)
PEBPs1
It was also revealed that IC had the ligand-binding site, which is conserved among PEBPs and the putative binding site of the polar head group of phospholipid. (nih.gov)
Promoter1
In addition, we studied hypermethylation of the promoter region of RKIP as a mechanism for loss of RKIP expression in MMR-proficient and MMR-deficient CRCs. (medscape.com)
Tissue2
Immunohistochemical staining for RKIP was performed on a tissue microarray comprising 1,197 mismatch repair (MMR)-proficient and 141 MMR-deficient CRCs. (medscape.com)
In this study, we documented the prognostic significance of cytoplasmic expression of RKIP in 1,197 mismatch repair (MMR)-proficient colorectal cancers (CRCs) randomized into 2 subgroups (n = 599 and n = 598) and in 141 MMR-deficient CRCs using tissue microarray (TMA) technology and a simple and reproducible scoring system. (medscape.com)
Shown1
Phosphatidylethanolamine binding protein 1 has been shown to interact with: C-Raf, MAP2K1, and MAPK1. (wikipedia.org)
Regulation1
Raf-1 kinase inhibitor protein: structure, function, regulation of cell signaling, and pivotal role in apoptosis. (wikipedia.org)
Levels1
Here, we show that RKIP binds GSK3 proteins and maintains GSK3ß protein levels and its active form. (aston.ac.uk)
Role1
[ 7 ] Initial studies showed that RKIP achieves this role by competitive interference with the binding of MEK to Raf-1. (medscape.com)
Results1
[ 13 ] These results suggest that RKIP has no major impact on primary tumorigenesis but functions as a suppressor of metastasis. (medscape.com)
Potential1
These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression. (aston.ac.uk)
Loss5
Chromosomal instability was assessed using metaphase-based comparative genomic hybridisation (CGH) and loss of heterozygosity (LOH) in 65 cases with microsatellite stable CRC and correlated with RKIP expression. (bmj.com)
Loss of cytoplasmic RKIP was associated with distant metastasis ( P = .038), higher N stage ( P = .032), vascular invasion ( P = .01), and worse survival ( P = .001) in the MMR-proficient group. (medscape.com)
In MMR-deficient CRCs, loss of cytoplasmic RKIP was associated with distant metastasis ( P = .043) and independently predicted worse survival ( P = .004). (medscape.com)
Loss of RKIP expression is a marker of tumor progression and distant metastasis in MMR-proficient and MMR-deficient CRCs. (medscape.com)
An association between loss of RKIP expression and metastatic progression has also been documented in patients with melanoma, prostate cancer, and breast cancer. (medscape.com)
Activation1
What's more, RKIP can bind to the N-region of the Raf-1 kinase domain therebye inhibiting its activation. (axonmedchem.com)
Features1
The association of RKIP with clinicopathologic features was analyzed. (medscape.com)
Study1
This study presents a novel discovery approach based on serum immunoprecipitation with cancer-specific in vivo biotinylated recombinant antibodies (biobodies) derived from differentially selected yeast-display scFv, and analysis of the eluted serum proteins by electrophoresis and/or mass spectrometry. (nih.gov)
Analysis1
Classes for this protein according to Protein ANalysis THrough Evolutionary Relationships (PANTHER) Classification System. (nih.gov)
Cells2
In breast and prostate cancers, ectopic expression of RKIP sensitized cells to chemotherapeutic-induced apoptosis, and reduced expression of RKIP led to resistance to chemotherapy. (medscape.com)
[ 13 ] Restoration of RKIP expression in metastatic prostate cancer cells inhibited invasiveness of the cells in vitro and in vivo in spontaneous lung metastasis but not the growth of the primary tumor in a murine model. (medscape.com)