Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction Journal Article
| Authors: | Liang, X.; Nazarian, A.; Erdjument-Bromage, H.; Bornmann, W.; Tempst, P.; Resh, M. D. |
| Article Title: | Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction |
| Abstract: | Fatty acylation of Src family kinases is essential for localization of the modified proteins to the plasma membrane and to plasma membrane rafts. It has been suggested that the presence of saturated fatty acyl chains on proteins is conducive for their insertion into liquid ordered lipid domains present in rafts. The ability of unsaturated dietary fatty acids to be attached to Src family kinases has not been investigated. Here we demonstrate that heterogeneous fatty acylation of Src family kinases occurs and that the nature of the attached fatty acid influences raft-mediated signal transduction. By using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we show that in addition to 14:0 (myristate), 14:1 and 14:2 fatty acids can be attached to the N-terminal glycine of the Src family kinase Fyn when the growth media are supplemented with these dietary fatty acids. Moreover, we synthesized novel iodinated analogs of oleate and stearate, and we showed that heterogeneous S-acylation can occur on cysteine residues within Fyn as well as Gα, GAP43, and Ras. Modification of Fyn with unsaturated or polyunsaturated fatty acids reduced its raft localization and resulted in decreased T cell signal transduction. These studies establish that heterogeneous fatty acylation is a widespread occurrence that serves to regulate signal transduction by membrane-bound proteins. |
| Keywords: | signal transduction; controlled study; carrier protein; unclassified drug; oncoprotein; human cell; proto-oncogene proteins; nonhuman; protein domain; protein localization; proteins; animal cell; animal; metabolism; animals; protein; membrane proteins; protein tyrosine kinase; cos cells; animalia; biosynthesis; carrier proteins; membrane protein; cell membrane; cell strain cos1; adaptor proteins, signal transducing; phosphoproteins; ras protein; lipids; fatty acids; src-family kinases; fatty acid; phosphotransferase; signal transducing adaptor protein; neuromodulin; phosphoprotein; cysteine; glycine; leukemia cell line; jurkat cells; protein modification; acylation; cells; rabbits; fat intake; protein kinase fyn; proto-oncogene proteins c-fyn; myristic acid; myristylation; membrane microdomains; oleic acid; ionization; rabbit; saturated fatty acid; fatty acylation; biological membranes; desorption; polyunsaturated fatty acid; fatty acids, unsaturated; heterogeneous fatty acylation; src family kinase; stearic acid; unsaturated fatty acid; humans; human; priority journal; article; insertion sequences; matrix-assisted laser desorption; guanine nucleotide binding protein alpha; fyn protein, human; lat protein, human; liquid ordered lipid domain; plasma membrane raft localization; raft mediated signal transduction |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 276 |
| Issue: | 33 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2001-08-17 |
| Start Page: | 30987 |
| End Page: | 30994 |
| Language: | English |
| DOI: | 10.1074/jbc.M104018200 |
| PUBMED: | 11423543 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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