title: The Ca2+-dependent lipid binding domain of P120GAP mediates protein-protein interactions with Ca2+-dependent membrane-binding proteins. Evidence for a direct interaction between annexin VI and P120GAP.
abstract: The CaLB domain is a 43-amino acid sequence motif found in a number of functionally diverse signaling proteins including three Ras-specific GTPase activating proteins (GAPs). In the Ras GTPase activating protein, P120(GAP), this domain has the ability to confer membrane association in response to intracellular Ca2+ elevation. Here we have isolated three proteins, p55, p70, and p120, which interact with the P120(GAP) CaLB domain in vitro. We identify p70 as the Ca2+-dependent phospholipid-binding protein annexin VI. Using co-immunoprecipitation studies, we have shown that the interaction between P120(GAP) and annexin VI is also detectable in rat fibroblasts, suggesting that this interaction may have a physiological role in vivo. Thus, the CaLB domain in P120(GAP) appears to have the ability to direct specific protein-protein interactions with Ca2+-dependent membrane-associated proteins. In addition, annexin VI is known to have tumor suppressor activity. Therefore, it is possible that the interaction of annexin VI with P120(GAP) may be important in the subsequent modulation of p21(ras) activity.
authors.affiliation: Department of Pharmacology, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: A J
authors.initials: AJ
authors.lastname: Davis
authors.forename: J T
authors.initials: JT
authors.lastname: Butt
authors.forename: J H
authors.initials: JH
authors.lastname: Walker
authors.forename: S E
authors.initials: SE
authors.lastname: Moss
authors.forename: D J
authors.initials: DJ
authors.lastname: Gawler
mesh_terms: D000818:Animals; D017317:Annexin A6 / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D020690:GTPase-Activating Proteins; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D020703:ras GTPase-Activating Proteins
chemical_list: D017317:Annexin A6; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D002118:Calcium