Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/60684
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Translocation of sphingosine kinase 1 to the plasma membrane is mediated by calcium- and integrin-binding protein 1 |
Author: | Jarman, K. Moretti, P. Zebol, J. Pitson, S. |
Citation: | Journal of Biological Chemistry, 2010; 285(1):483-492 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2010 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | Kate E. Jarman, Paul A. B. Moretti, Julia R. Zebol and Stuart M. Pitson |
Abstract: | SK1 (sphingosine kinase 1) plays an important role in many aspects of cellular regulation. Most notably, elevated cellular SK1 activity leads to increased cell proliferation, protection from apoptosis, and induction of neoplastic transformation. We have previously shown that translocation of SK1 from the cytoplasm to the plasma membrane is integral for oncogenesis mediated by this enzyme. The molecular mechanism mediating this translocation of SK1 has remained undefined. Here, we demonstrate a direct role for CIB1 (calcium and integrin-binding protein 1) in this process. We show that CIB1 interacts with SK1 in a Ca2+-dependent manner at the previously identified “calmodulin-binding site” of SK1. We also demonstrate that CIB1 functions as a Ca2+-myristoyl switch, providing a mechanism whereby it translocates SK1 to the plasma membrane. Both small interfering RNA knockdown of CIB1 and the use of a dominant-negative CIB1 we have generated prevent the agonist-dependent translocation of SK1. Furthermore, we demonstrate the requirement of CIB1-mediated translocation of SK1 in controlling cellular sphingosine 1-phosphate generation and associated anti-apoptotic signaling. |
Keywords: | Cell Line, Tumor Cell Membrane Humans Calcium Phosphotransferases (Alcohol Group Acceptor) Myristic Acid Tumor Necrosis Factor-alpha Calcium-Binding Proteins Calmodulin NF-kappa B Apoptosis Binding Sites Protein Binding Protein Transport Genes, Dominant Gene Knockdown Techniques |
Rights: | © 2010 by The American Society for Biochemistry and Molecular Biology |
DOI: | 10.1074/jbc.M109.068395 |
Published version: | http://dx.doi.org/10.1074/jbc.m109.068395 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.