Epidermal growth factor-dependent phosphorylation of the GGA3 adaptor protein regulates its recruitment to membranes.

The Golgi-localized, Gamma-ear-containing, Arf-binding (GGA) proteins are monomeric clathrin adaptors that mediate the sorting of transmembrane cargo at the trans-Golgi network and endosomes. Here we report that one of these proteins, GGA3, becomes transiently phosphorylated upon activation of the epidermal growth factor (EGF) receptor. This phosphorylation takes place on a ...
previously unrecognized site in the "hinge" segment of the protein, S368, and is strictly dependent on the constitutive phosphorylation of another site, S372. The EGF-induced phosphorylation of S368 does not require internalization of the EGF receptor or association of GGA3 with membranes. This phosphorylation can be blocked by inhibitors of both the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways that function downstream of the activated EGF receptor. Phosphorylation of GGA3 on S368 causes an increase in the hydrodynamic radius of the protein, indicating a transition to a more asymmetric shape. Mutation of S368 and S372 to a phosphomimic aspartate residue decreases the association of GGA3 with membranes. These observations indicate that EGF signaling elicits phosphorylation events that regulate the association of GGA3 with organellar membranes.
Mesh Terms:
ADP-Ribosylation Factors, Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Cells, Cultured, Humans, Intracellular Membranes, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Mutation, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein Transport, Receptor, Epidermal Growth Factor, Signal Transduction
Mol. Cell. Biol.
Date: Sep. 01, 2005
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