SRC-mediated phosphorylation of dynamin and cortactin regulates the "constitutive" endocytosis of transferrin.
The mechanisms by which epithelial cells regulate clathrin-mediated endocytosis (CME) of transferrin are poorly defined and generally viewed as a constitutive process that occurs continuously without regulatory constraints. In this study, we demonstrate for the first time that endocytosis of the transferrin receptor is a regulated process that requires activated Src kinase and, subsequently, phosphorylation of two important components of the endocytic machinery, namely, the large GTPase dynamin 2 (Dyn2) and its associated actin-binding protein, cortactin (Cort). To our knowledge these findings are among the first to implicate an Src-mediated endocytic cascade in what was previously presumed to be a nonregulated internalization process.
Cao
Hong
H
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Chen
Jing
J
Krueger
Eugene W
EW
McNiven
Mark A
MA
D000818:Animals; D002460:Cell Line; D051356:Cortactin / Q000819:agonists / Q000378:metabolism*; D034285:Dynamin II / Q000819:agonists / Q000378:metabolism*; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism*
D051356:Cortactin; D011990:Receptors, Transferrin; C545564:Tfrc protein, rat; D014168:Transferrin; D019061:src-Family Kinases; D034285:Dynamin II