THE PRODUCT OF THE MLD GENE IS A MEMBER OF THE MEMBRANE FATTY-ACID DESATURASE FAMILY - OVEREXPRESSION OF MLD INHIBITS EGF RECEPTOR BIOSYNTHESIS

Membrane fatty acid desaturases are responsible for inserting double b onds into specific positions in fatty acids. We have cloned a new memb er of the human membrane fatty acid (lipid) desaturase gene family, ML D. The derived amino acid sequence of MLD contains three consensus mot ifs, HX3H, HX2HH, and HX2HHXFP, that are characteristic of a group of membrane fatty acid desaturases. MLD is predicted to be a multiple mem brane-spanning protein and is found to be extractable from particulate fractions with detergent but not salt or urea. MLD is widely expresse d in human tissues and is localized to the endoplasmic reticulum. Cotr ansfection of MLD with the epidermal growth factor (EGF) receptor resu lted in decreased expression of the receptor but did not affect platel et-derived growth factor receptor expression. MLD overexpression inhib ited biosynthesis of the EGF receptor, suggesting a possible role of a fatty acid desaturase in regulating biosynthetic processing of the EG F receptor.