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A novel six-transmembrane protein hhole functions as a suppressor in MAPK signaling pathways.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2005 Jul 29; Vol. 333 (2), pp. 344-52. - Publication Year :
- 2005
-
Abstract
- Src homology 3 (SH3) domains mediate intracellular protein-protein interactions through the recognition of proline-rich sequence motifs on cellular proteins. Such protein-protein interactions can activate the protein kinase cascade that mediates MAPK signaling pathway. The human hole gene, hhole, is a 319-amino acid six-transmembrane protein with proline-rich C-terminal motifs and N-terminal ERK binding domains (D-domains). The hhole protein is highly conserved in evolution across different species from elegent, mouse to human. Northern blot analysis indicates that hhole is expressed in heart, liver, skeletal muscle, and pancreas at adult stages and in most of the examined embryonic tissues, especially at a higher level in heart. Using a GFP-labeled hhole protein, we demonstrate that hhole is localized in plasma membrane or proximal region of the membrane. Overexpression of hhole in COS-7 cells strongly inhibited the transcriptional activities of AP-1 and SRE while deletion of the C-terminal proline-rich motifs or the N-terminal ERK binding D-domain motifs reduced the repressive activity of the gene. These results suggest that the hhole protein may interact with SH3-domain proteins or ERKs to mediate signaling pathways/networks that lead to the suppression of AP-1 and SRE.
- Subjects :
- Amino Acid Sequence
Animals
COS Cells
Chlorocebus aethiops
Gene Expression Regulation, Enzymologic physiology
Humans
Intracellular Signaling Peptides and Proteins analysis
Intracellular Signaling Peptides and Proteins genetics
Membrane Proteins analysis
Membrane Proteins genetics
Molecular Sequence Data
Organ Specificity
Recombinant Proteins metabolism
Sequence Homology, Amino Acid
Tissue Distribution
Transcriptional Activation physiology
src Homology Domains
DNA-Binding Proteins metabolism
Intracellular Signaling Peptides and Proteins chemistry
Intracellular Signaling Peptides and Proteins metabolism
Membrane Proteins chemistry
Membrane Proteins metabolism
Mitogen-Activated Protein Kinases metabolism
Signal Transduction physiology
Transcription Factor AP-1 metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 333
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 15950185
- Full Text :
- https://doi.org/10.1016/j.bbrc.2005.05.115