Sequence homology of rat and human HCNP precursor proteins, bovine phosphatidylethanolamine-binding protein and rat 23-kDa protein associated with the opioid-binding protein

Tohdoh, Naoki; Tojo, Shinichiro J.; Agui, Hideo; Ojika, Kosei

doi:10.1016/0169-328x(95)00029-r

Cited by 75 publications

(46 citation statements)

References 7 publications

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“…This family is an evolutionarily conserved group found in species of flowering plants (Antirrhinum (1)), parasites (Plasmodium falciparium (2)), nematodes (Toxocara canis (3)), insects (Drosophila melanogaster (4)), and mammals, including cattle, monkeys, and humans (5). A number of functions have been suggested for the mammalian PEBP proteins, including lipid binding and inhibition of serine proteases (6).…”

mentioning

confidence: 99%

“…A number of functions have been suggested for the mammalian PEBP proteins, including lipid binding and inhibition of serine proteases (6). These proteins can also act as precursors for a bioactive peptide HCNP (hippocampal cholinergic neurostimulating peptide), important in hippocampus development (5). Plant PEBP homologues are involved in the control of a morphogenic switch between shoot growth and flower structures (7).…”

mentioning

confidence: 99%

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A Novel Human Phosphatidylethanolamine-binding Protein Resists Tumor Necrosis Factor α-induced Apoptosis by Inhibiting Mitogen-activated Protein Kinase Pathway Activation and Phosphatidylethanolamine Externalization

Wang

Liu

et al. 2004

Journal of Biological Chemistry

115

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The phosphatidylethanolamine (PE)-binding proteins (PEBPs) are an evolutionarily conserved family of proteins with pivotal biological functions. Here we describe the cloning and functional characterization of a novel family member, human phosphatidylethanolaminebinding protein 4 (hPEBP4). hPEBP4 is expressed in most human tissues and highly expressed in tumor cells. Its expression in tumor cells is further enhanced upon tumor necrosis factor (TNF) ␣ treatment, whereas hPEBP4 normally co-localizes with lysosomes, TNF␣ stimulation triggers its transfer to the cell membrane, where it binds to Raf-1 and MEK1. L929 cells overexpressing hPEBP4 are resistant to both TNF␣-induced ERK1/2, MEK1, and JNK activation and TNF␣-mediated apoptosis. Co-precipitation and in vitro protein binding assay demonstrated that hPEBP4 interacts with Raf-1 and MEK1. A truncated form of hPEBP4, lacking the PE-binding domain, maintains lysosomal co-localization but has no effect on cellular responses to TNF␣. Given that MCF-7 breast cancer cells expressed hPEBP4 at a high level, small interfering RNA was used to silence the expression of hPEBP4. We demonstrated that down-regulation of hPEBP4 expression sensitizes MCF-7 breast cancer cells to TNF␣-induced apoptosis. hPEBP4 appears to promote cellular resistance to TNF-induced apoptosis by inhibiting activation of the Raf-1/MEK/ERK pathway, JNK, and PE externalization, and the conserved region of PE-binding domain appears to play a vital role in this biological activity of hPEBP4.The phosphatidylethanolamine-binding protein (PEBP) 1 family consists of a number of 21-23-kDa basic proteins, first identified in bovine brain, with preferential in vitro affinity for phosphatidylethanolamine, a component of the cell membrane. This family is an evolutionarily conserved group found in species of flowering plants (Antirrhinum (1)), parasites (Plasmodium falciparium (2)), nematodes (Toxocara canis (3)), insects (Drosophila melanogaster (4)), and mammals, including cattle, monkeys, and humans (5). A number of functions have been suggested for the mammalian PEBP proteins, including lipid binding and inhibition of serine proteases (6). These proteins can also act as precursors for a bioactive peptide HCNP (hippocampal cholinergic neurostimulating peptide), important in hippocampus development (5). Plant PEBP homologues are involved in the control of a morphogenic switch between shoot growth and flower structures (7). Yeast two-hybrid screen analysis has shown that human PEBP1 (hPEBP1, also called Raf kinase inhibitory protein or RKIP) acts as a suppressor of Raf-1 kinase activity and mitogen-activated protein kinase signaling in fibroblasts via its ability to sequester and inactivate Raf-1 and MEK1 (8, 9). Both Raf-1 and MEK bind to the highly conserved phosphatidylethanolamine-binding domain of hPEBP; hPEBP induces dissociation of Raf-1⅐MEK complexes and behaves as a competitive inhibitor of MEK phosphorylation. Mapping of the binding domains has shown that MEK and Raf-1 bind to overlapping sites in hPEBP...

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confidence: 99%

mentioning

confidence: 99%

A Novel Human Phosphatidylethanolamine-binding Protein Resists Tumor Necrosis Factor α-induced Apoptosis by Inhibiting Mitogen-activated Protein Kinase Pathway Activation and Phosphatidylethanolamine Externalization

Wang

Liu

et al. 2004

Journal of Biological Chemistry

115

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“…It has been suggested that RKIP-1 protein is a precursor of HCNP [29,30,37]. The reporter expression pattern in the mouse brain is consistent with potential endocrine relevance of the gene [1,15].…”

Section: Discussionsupporting

confidence: 53%

Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

Theroux

Pereira

Casten

et al. 2007

Brain Research Bulletin

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Raf Kinase Inhibitory Protein (RKIP-1) is involved in the regulation of the MAP kinase, NF-κB, and GPCR signaling pathways. It is expressed in numerous tissues and cell types and orthologues have been documented throughout the animal and plant kingdoms. RKIP-1 has also been reported as an inhibitor of serine proteases, and a precursor of a neurostimulatory peptide. RKIP-1 has been implicated as a suppressor of metastases in several human cancers. We generated a knockout strain of mice to further assess RKIP-1's function in mammals. RKIP-1 is expressed in many tissues with the highest protein levels detectable in testes and brain. In the brain, expression was ubiquitous in limbic formations, and homozygous mice developed olfaction deficits in the first year of life. We postulate that RKIP-1 may be a modulator of behavioral responses.

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“…The PEBP family regulates signaling pathways to control growth and differentiation. PEBPs are neural peptide precursors, protease and kinase inhibitors, and Ras-signaling modulators (25)(26)(27)(28)(29). Studies on the mammalian homologue Raf-kinase inhibitor protein (RKIP) show that it modulates Raf action, G-protein signaling, and NF-B activity (30)(31)(32)(33).…”

Section: Flowering Locus T ͉ Phosphatidylethanolamine-binding Protein ͉mentioning

confidence: 99%

A single amino acid converts a repressor to an activator of flowering

Hanzawa

Money

Bradley

2005

Proc. Natl. Acad. Sci. U.S.A.

453

428

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Homologous proteins occurring through gene duplication may give rise to novel functions through mutations affecting protein sequence or expression. Comparison of such homologues allows insight into how morphological traits evolve. However, it is often unclear which changes are key to determining new functions. To address these ideas, we have studied a system where two homologues have evolved clear and opposite functions in controlling a major developmental switch. In plants, flowering is a major developmental transition that is critical to reproductive success. Arabidopsis phosphatidylethanolamine-binding protein homologues TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) are key controllers of flowering, determining when and where flowers are made, but as opposing functions: TFL1 is a repressor, FT is an activator. We have uncovered a striking molecular basis for how these homologous proteins have diverged. Although <60% identical, we have shown that swapping a single amino acid is sufficient to convert TFL1 to FT function and vice versa. Therefore, these key residues may have strongly contributed to the selection of these important functions over plant evolution. Further, our results suggest that TFL1 and FT are highly conserved in biochemical function and that they act as repressors or activators of flowering through discrimination of structurally related interactors by a single residue. FLOWERING LOCUS T ͉ phosphatidylethanolamine-binding protein ͉Raf-kinase inhibitor protein ͉ TERMINAL FLOWER 1 N ovel morphologies arise through the evolution of new protein functions. Duplicated genes are a key source of new functions, acquiring mutations that affect expression and͞or protein sequence (1, 2). Studies of large gene families show that different members diverge and participate in different developmental pathways, for example, homeobox and MADS box genes in various species (3-5). However, it is often unclear and difficult to determine which changes in homologues are critical to establish a novel function.The Arabidopsis homologues TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) provide an excellent model to address this question (6-9). Flowering plant species arose Ͼ 100 million years ago, and FT and TFL1 have been conserved in diverse species, including monocots and eudicots (10-15). Both TFL1 and FT are key controllers of flowering and plant architecture but act in an opposite manner. TFL1 is a repressor, and FT is an activator. Further, gain-of-function studies gave clear and opposite phenotypes in vivo, showing that protein sequence, rather than expression pattern, largely determines the different functions of TFL1 and FT (8,9,16).TFL1 is expressed in the shoot apical meristem (SAM) and represses the transition to flowering; tfl1 mutants flower early (6,7,17,18). TFL1 also maintains indeterminate growth of the SAM by repressing floral meristem identity genes; tfl1 mutants have their SAMs converted into terminal flowers. TFL1 therefore controls plant architecture by determining where flowers are made a...

show abstract

Sequence homology of rat and human HCNP precursor proteins, bovine phosphatidylethanolamine-binding protein and rat 23-kDa protein associated with the opioid-binding protein

Cited by 75 publications

References 7 publications

A Novel Human Phosphatidylethanolamine-binding Protein Resists Tumor Necrosis Factor α-induced Apoptosis by Inhibiting Mitogen-activated Protein Kinase Pathway Activation and Phosphatidylethanolamine Externalization

A Novel Human Phosphatidylethanolamine-binding Protein Resists Tumor Necrosis Factor α-induced Apoptosis by Inhibiting Mitogen-activated Protein Kinase Pathway Activation and Phosphatidylethanolamine Externalization

Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

A single amino acid converts a repressor to an activator of flowering

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