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PMID:12009895

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Citation

Sun, J, Nanjundan, M, Pike, LJ, Wiedmer, T and Sims, PJ (2002) Plasma membrane phospholipid scramblase 1 is enriched in lipid rafts and interacts with the epidermal growth factor receptor. Biochemistry 41:6338-45

Abstract

We have identified physical and functional interactions between the epidermal growth factor (EGF) receptor and phospholipid scramblase 1 (PLSCR1), an endofacial plasma membrane protein proposed to affect phospholipid organization. PLSCR1, a palmitoylated protein, was found to partition with the EGF receptor in membrane lipid rafts. Cell stimulation with EGF transiently elevated Tyr-phosphorylation of PLSCR1, peaking at 5 min. Although PLSCR1 is a known substrate of c-Abl [Sun, J., et al. (2001) J.Biol. Chem. 276, 28984-28990], the Abl inhibitor STI571 did not substantially affect its EGF-dependent phosphorylation, suggesting PLSCR1 is a substrate of the EGF receptor kinase, or another EGF-activated kinase. Coinciding with phosphorylation, there was a transient increase in physical association of PLSCR1 with both the EGF receptor and the adapter protein Shc, as determined by immunoprecipitation and Western blotting. Confocal immunofluorescence analysis revealed that EGF initiates rapid internalization of both the EGF receptor and PLSCR1, with trafficking into both distinct and common endosomal pools. These data also suggested that whereas the EGF receptor is ultimately degraded, much of the endocytosed PLSCR1 is recycled to the cell surface within 3 h after EGF treatment. Consistent with this interpretation, Western blotting revealed neither ubiquitination nor proteolysis of PLSCR1 under these conditions, whereas the ubiquitination and degradation of the EGF receptor were readily confirmed. Finally, stimulation with EGF was also found to markedly increase the total cellular expression of PLSCR1, suggesting that in addition to its initial interactions with activated EGF receptor, PLSCR1 may also contribute to posttranscriptional effector pathway(s) mediating the cellular response to EGF.

Links

PubMed

Keywords

Carrier Proteins/biosynthesis; Carrier Proteins/metabolism; Carrier Proteins/physiology; Endocytosis/physiology; Epidermal Growth Factor/pharmacology; Humans; KB Cells; Membrane Microdomains/enzymology; Membrane Microdomains/metabolism; Membrane Proteins/biosynthesis; Membrane Proteins/metabolism; Membrane Proteins/physiology; Phospholipid Transfer Proteins; Phospholipids/metabolism; Phosphorylation; Phosphotyrosine/metabolism; Proto-Oncogene Proteins c-abl/physiology; Receptor, Epidermal Growth Factor/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PLS1

part_of

GO:0045121: membrane raft

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PLS1

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P00533

F

Seeded From UniProt

complete

HUMAN:EGFR

part_of

GO:0045121: membrane raft

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:EGFR

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O15162

F

Seeded From UniProt

complete


See also

References

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