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: A J Davis, J T Butt, J H Walker, S E Moss, D J Gawler
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 271 Issue 40 Pg. 24333-6 (Oct 04 1996) ISSN: 0021-9258 [Print] United States
• PMID: 8798684 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A6
• GTPase-Activating Proteins
• Membrane Proteins
• Proteins
• ras GTPase-Activating Proteins
• Calcium

Topics

• Animals
• Annexin A6 (metabolism)
• Calcium (metabolism)
• Cell Line
• GTPase-Activating Proteins
• Lipid Metabolism
• Membrane Proteins (metabolism)
• Protein Binding
• Proteins (metabolism)
• Rats
• Signal Transduction
• ras GTPase-Activating Proteins