title: C-terminal domain of the Epstein-Barr virus LMP2A membrane protein contains a clustering signal.
abstract: The latency-regulated transmembrane protein LMP2A interferes with signaling from the B-cell antigen receptor by recruiting the tyrosine kinases Lyn and Syk and by targeting them for degradation by binding the cellular E3 ubiquitin ligase AIP4. It has been hypothesized that this constitutive activity of LMP2A requires clustering in the membrane, but molecular evidence for this has been lacking. In the present study we show that LMP2A coclusters with chimeric rat CD2 transmembrane molecules carrying the 27-amino-acid (aa) intracellular C terminus of LMP2A and that this C-terminal domain fused to the glutathione-S-transferase protein associates with LMP2A in cell lysates. This molecular association requires neither the cysteine-rich region between aa 471 and 480 nor the terminal three aa 495 to 497. We also show that the juxtamembrane cysteine repeats in the LMP2A C terminus are the major targets for palmitoylation but that this acylation is not required for targeting of LMP2A to detergent-insoluble glycolipid-enriched membrane microdomains.
authors.affiliation: Karolinska Institutet, Microbiology and Tumor Biology Center (MTC), SE-171 77 Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Matskova
authors.forename: I
authors.initials: I
authors.lastname: Ernberg
authors.forename: T
authors.initials: T
authors.lastname: Pawson
authors.forename: G
authors.initials: G
authors.lastname: Winberg
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine; D021962:Membrane Microdomains / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D017830:Octoxynol / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000502:physiology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D014763:Viral Matrix Proteins; D019308:Palmitic Acid; D017830:Octoxynol; D003545:Cysteine