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AGS3 TPR domain interacting protein 2 (ATIP‐2) influences AGS3 interaction with G‐protein.
Author(s) -
An Ningfei,
Blumer Joe,
Bernard Michael,
Chung Peter,
Lanier Stephen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a256-d
Subject(s) - pdz domain , ezrin , tetratricopeptide , microbiology and biotechnology , biology , fusion protein , moesin , cell fractionation , radixin , biochemistry , cytoskeleton , cell , gene , recombinant dna , membrane
A ctivator of G ‐protein s ignaling 3 (AGS3) has two distinct domains separated by a linker region in the middle of the protein. The carboxyl‐terminal half of the protein contains fourG‐protein regulatory (GPR) motifs that provide docking sites for G α i>G αo and the amino‐terminalhalf of the protein contains seven tetratricopeptide repeats (TPRs) with unknown function in this protein. ATIP‐2 ( A GS3 T PR domain interacting protein 2 ) Arg 1067 ‐Leu 1745 was identified in a yeast two‐hybrid screen of a rat adult brain library using the TPR‐linker region of AGS3 (Met 1 ‐Pro 463 ) as bait. ATIP‐2 (1745 amino acids) contains 1 PDZ ( P SD‐95, D iscs‐large, Z O‐1) domain and 1 FERM (band 4.1 ezrin‐radixin‐moesin homology) domain. A GST‐ATIP‐2 (Arg 1067 ‐Leu 1745 ) fusion protein pulled down AGS3 from rat brain lysates and subsequent truncation constructs localized the AGS3 binding region to Ala 1098 ‐Val 1135 . Full‐length ATIP‐2 and AGS3 coimmunoprecipitated following expression in COS7 cells and this interaction was inhibited by overexpression of Giα3 suggesting that the interaction of AGS3 with ATIP‐2 and Giα3 are mutually exclusive. Subcellular fractionation studies following COS7 cell transfection suggested that ATIP‐2 expression increased the proportion of AGS3 associated with a cell membrane fraction. These data suggests that ATIP‐2 plays a regulatory role in AGS3 function by influencing the subcellular location of AGS3 and its interaction with G‐proteins.