NDLI: Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity

Content Provider	PubMed Central
Author	Preger, Ella Ziv, Inbal Shabtay, Ariel Sher, Ifat Tsang, Michael Dawid, Igor B. Yael, Altuvia Ron, Dina
Copyright Year	2004
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.
Related Links	http://dx.doi.org/10.1073/pnas.0307952100
Starting Page	1229
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	101
Language	English
Publisher	National Academy of Sciences
Publisher Date	2004-02-03
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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