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פותח על ידי קלירמאש פתרונות בע"מ -
Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity
Year:
2004
Authors :
שבתאי, אריאל
;
.
Volume :
101
Co-Authors:
Preger, E., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Ziv, I., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Shabtay, A., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Sher, I., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Tsang, M., Laboratory of Molecular Genetics, Natl. Inst. of Child Hlth./Hum. Dev., National Institutes of Health, Bethesda, MD 20892, United States
Dawid, I.B., Laboratory of Molecular Genetics, Natl. Inst. of Child Hlth./Hum. Dev., National Institutes of Health, Bethesda, MD 20892, United States
Altuvia, Y., Dept. of Molec. Genet. and Biotech., Hebrew University-Hadassah Med. Sch., Jerusalem 91120, Israel
Ron, D., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Facilitators :
From page:
1229
To page:
1234
(
Total pages:
6
)
Abstract:
Receptor tyrosine kinases (RTKs) control a multitude of biological processes and are therefore subjected to multiple levels of regulation. Negative feedback is one of the mechanisms that provide an effective means to control RTK-mediated signaling. Sef has recently been identified as a specific antagonist of fibroblast growth factor (FGF) signaling in zebrafish and subsequently in mouse and human. Sef encodes a putative type I transmembrane protein that antagonizes the Ras/mitogen-activated protein kinase pathway in all three species. Mouse Sef was also shown to inhibit the phosphatidylinositol 3-kinase pathway. We show here that an alternative splicing mechanism generates an isoform of human Sef, hSef-b, which unlike the previously reported Sef (hSef-a) is a cytosolic protein. Contrary to hSef-a, which is ubiquitously expressed, hSef-b transcripts display a restricted pattern of expression in human tissues. hSef-b inhibits FGF-induced cell proliferation and prevents the activation of mitogen-activated protein kinase without affecting the upstream component MAPK kinase. Furthermore, hSef-b does not antagonize FGF induction of the phosphatidylinositol 3-kinase pathway. In addition to the effects on FGF signaling, hSef-b inhibited cellular response to platelet-derived growth factor but not other RTK ligands. Therefore, alternative splicing of the hSef gene expands the Sef feedback inhibition repertoire of RTK signaling.
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עוד תגיות
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More details
DOI :
10.1073/pnas.0307952100
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
31335
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 01:01
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Scientific Publication
Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity
101
Preger, E., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Ziv, I., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Shabtay, A., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Sher, I., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Tsang, M., Laboratory of Molecular Genetics, Natl. Inst. of Child Hlth./Hum. Dev., National Institutes of Health, Bethesda, MD 20892, United States
Dawid, I.B., Laboratory of Molecular Genetics, Natl. Inst. of Child Hlth./Hum. Dev., National Institutes of Health, Bethesda, MD 20892, United States
Altuvia, Y., Dept. of Molec. Genet. and Biotech., Hebrew University-Hadassah Med. Sch., Jerusalem 91120, Israel
Ron, D., Department of Biology, Technion-Israel Inst. of Technology, Haifa 32000, Israel
Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity
Receptor tyrosine kinases (RTKs) control a multitude of biological processes and are therefore subjected to multiple levels of regulation. Negative feedback is one of the mechanisms that provide an effective means to control RTK-mediated signaling. Sef has recently been identified as a specific antagonist of fibroblast growth factor (FGF) signaling in zebrafish and subsequently in mouse and human. Sef encodes a putative type I transmembrane protein that antagonizes the Ras/mitogen-activated protein kinase pathway in all three species. Mouse Sef was also shown to inhibit the phosphatidylinositol 3-kinase pathway. We show here that an alternative splicing mechanism generates an isoform of human Sef, hSef-b, which unlike the previously reported Sef (hSef-a) is a cytosolic protein. Contrary to hSef-a, which is ubiquitously expressed, hSef-b transcripts display a restricted pattern of expression in human tissues. hSef-b inhibits FGF-induced cell proliferation and prevents the activation of mitogen-activated protein kinase without affecting the upstream component MAPK kinase. Furthermore, hSef-b does not antagonize FGF induction of the phosphatidylinositol 3-kinase pathway. In addition to the effects on FGF signaling, hSef-b inhibited cellular response to platelet-derived growth factor but not other RTK ligands. Therefore, alternative splicing of the hSef gene expands the Sef feedback inhibition repertoire of RTK signaling.
Scientific Publication
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