Identification of 14-3-3zeta as an EGF receptor interacting protein.
The 14-3-3 proteins are known to interact with a number of proteins involved in the regulation of cell signaling. Here, we describe an association of 14-3-3zeta with the epidermal growth factor receptor (EGFR) that is rapidly induced by EGF. The 1028-EGFR truncated mutant which lacks the cytoplasmic tail from amino acids 1029-1186 identified the binding site for 14-3-3 to be between amino acid 1028 and the receptor carboxyl terminus. Mutational deletion of serine residues 1046, 1047, 1057 and 1142 did not inhibit EGF-induced 14-3-3 association with the receptor. Immunofluorescence microscopy indicated an EGF-induced co-localization of EGFR and HA-14-3-3zeta along the plasma membrane. Our finding adds to the growing complexity of EGF receptor signaling and indicates a role for 14-3-3 proteins in EGF receptor signaling or regulation.
Oksvold
Morten P
MP
Institute of Pathology, Rikshospitalet University Hospital, University of Oslo, N-0027 Oslo, Norway. m.p.oksvold@labmed.uio.no
Huitfeldt
Henrik S
HS
Langdon
Wallace Y
WY
D048948:14-3-3 Proteins; D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010741:Phospholipases A / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D048948:14-3-3 Proteins; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D014446:Tyrosine 3-Monooxygenase; D066246:ErbB Receptors; D010741:Phospholipases A