| First Author | Hawash IY | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 7 | Pages | 5683-91 |
| PubMed ID | 11741956 | Mgi Jnum | J:230372 |
| Mgi Id | MGI:5758825 | Doi | 10.1074/jbc.M110002200 |
| Citation | Hawash IY, et al. (2002) The Lck SH3 domain negatively regulates localization to lipid rafts through an interaction with c-Cbl. J Biol Chem 277(7):5683-91 |
| abstractText | Lck is a member of the Src family of protein-tyrosine kinases and is essential for T cell development and function. Lck is localized to the inner surface of the plasma membrane and partitions into lipid rafts via dual acylation on its N terminus. We have tested the role of Lck binding domains in regulating Lck localization to lipid rafts. A form of Lck containing a point mutation inactivating the SH3 domain (W97ALck) was preferentially localized to lipid rafts compared with wild type or SH2 domain-inactive (R154K) Lck when expressed in Lck-deficient J.CaM1 cells. W97ALck incorporated more of the radioiodinated version of palmitic acid, 16-[(125)I]iodohexadecanoic acid. Overexpression of c-Cbl, a ligand of the Lck SH3 domain, depleted Lck from lipid rafts in Jurkat cells. Additionally, Lck localization to lipid rafts was enhanced in c-Cbl-deficient T cells. The association of Lck with c-Cbl in vivo required a functional SH3 domain. These results suggest a model whereby the SH3 domain negatively regulates basal localization of Lck to lipid rafts via association with c-Cbl. |
