PMID- 10228163
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20220225
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 9
DP  - 1999 May 4
TI  - Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by
      dominant-negative mutant mu2 subunit and its effects on endocytosis.
PG  - 2489-99
AB  - Although interactions between the mu2 subunit of the clathrin adaptor protein
      complex AP-2 and tyrosine-based internalization motifs have been implicated in
      the selective recruitment of cargo molecules into coated pits, the functional
      significance of this interaction for endocytosis of many types of membrane
      proteins remains unclear. To analyze the function of mu2-receptor interactions,
      we constructed an epitope-tagged mu2 that incorporates into AP-2 and is targeted 
      to coated pits. Mutational analysis revealed that Asp176 and Trp421 of mu2 are
      involved in the interaction with internalization motifs of TGN38 and epidermal
      growth factor (EGF) receptor. Inducible overexpression of mutant mu2, in which
      these two residues were changed to alanines, resulted in metabolic replacement of
      endogenous mu2 in AP-2 complexes and complete abrogation of AP-2 interaction with
      the tyrosine-based internalization motifs. As a consequence, endocytosis of the
      transferrin receptor was severely impaired. In contrast, internalization of the
      EGF receptor was not affected. These results demonstrate the potential usefulness
      of the dominant-interfering approach for functional analysis of the adaptor
      protein family, and indicate that clathrin-mediated endocytosis may proceed in
      both a mu2-dependent and -independent manner.
FAU - Nesterov, A
AU  - Nesterov A
AD  - Department of Medicine, University of California at San Diego, La Jolla, CA
      92093, USA.
FAU - Carter, R E
AU  - Carter RE
FAU - Sorkina, T
AU  - Sorkina T
FAU - Gill, G N
AU  - Gill GN
FAU - Sorkin, A
AU  - Sorkin A
LA  - eng
GR  - CA 58689/CA/NCI NIH HHS/United States
GR  - CA46934/CA/NCI NIH HHS/United States
GR  - DK46817/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (AP1M2 protein, human)
RN  - 0 (AP3M2 protein, human)
RN  - 0 (Adaptor Protein Complex 1)
RN  - 0 (Adaptor Protein Complex 2)
RN  - 0 (Adaptor Protein Complex 3)
RN  - 0 (Adaptor Protein Complex alpha Subunits)
RN  - 0 (Adaptor Protein Complex mu Subunits)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (adaptor protein complex 1, mu 2 subunit)
RN  - 0 (adaptor protein complex 2, mu 2 subunit)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - *Adaptor Protein Complex 1
MH  - *Adaptor Protein Complex 2
MH  - *Adaptor Protein Complex 3
MH  - Adaptor Protein Complex alpha Subunits
MH  - *Adaptor Protein Complex mu Subunits
MH  - Adaptor Proteins, Vesicular Transport
MH  - Animals
MH  - Binding Sites
MH  - Biological Transport
MH  - Cell Compartmentation
MH  - Coated Pits, Cell-Membrane/metabolism
MH  - *Endocytosis
MH  - ErbB Receptors/metabolism
MH  - Humans
MH  - Membrane Proteins/genetics/*metabolism
MH  - Point Mutation
MH  - Protein Binding
MH  - Protein Engineering
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, Transferrin/metabolism
PMC - PMC1171331
EDAT- 1999/05/06 00:00
MHDA- 1999/05/06 00:01
CRDT- 1999/05/06 00:00
PHST- 1999/05/06 00:00 [pubmed]
PHST- 1999/05/06 00:01 [medline]
PHST- 1999/05/06 00:00 [entrez]
AID - 10.1093/emboj/18.9.2489 [doi]
PST - ppublish
SO  - EMBO J. 1999 May 4;18(9):2489-99. doi: 10.1093/emboj/18.9.2489.