- P-ISSN 1225-0163
- E-ISSN 2288-8985
IQ motif-containing GTPase-activating protein 1 (IQGAP1), which is a well-known Ca^(2+)-independent calmodulin (CaM) binding protein, is involved in various cellular functions such as cell proliferation and cell migration. IQGAP1 has four repeated IQ motifs, which are crucial for CaM binding. It has been shown that all four IQ motifs of IQGAP1 can bind to Ca^(2+)/CaM, while the third and fourth IQ motifs of IQGAP1 can bind to apoCaM. However, it has not been clear whether the CaM binding of IQ motifs of IQGAP1 was mediated directly or indirectly. In this study, we examined whether the binding between CaM and each IQ motif of IQGAP1 was direct in vitro. As a result, we found that IQ1 motif has a weak Ca^(2+)-dependent CaM binding. In contrast, IQ3 has a Ca^(2+)-dependent CaM binding. All other motifs have no significant CaM binding. We also found that IQ(2.7-3) and IQ(3.5-4.4) have CaM binding capacity. This finding indicates that IQ motifs of IQGAP1 plays a dynamic role via different motif interactions with Ca^(2+)/CaM or proCaM.
1. J. Noritake, T. Watanabe, K. Sato, S. Wang and K. Kaibuchi, J. Cell. Sci., 118(Pt 10), 2085-2092 (2005).
2. C. D. White, M. D. Brown and D. B. Sacks, FEBS Lett., 583(12), 1817-1824 (2009).
3. M. W. Briggs and D. B. Sacks, FEBS Lett., 542(1-3), 7-11 (2003).
4. Y. D. Ho, J. L. Joyal, Z. Li and D. B. Sacks, J. Biol. Chem., 274(1), 464-470 (1999).
5. Z. Li, S. H. Kim, J. M. Higgins, M. B. Brenner and D. B. Sacks, J. Biol. Chem., 274(53), 37885-37892 (1999).
6. M. W. Briggs, Z. Li and D. B. Sacks, J. Biol. Chem. 277(9), 7453-7465 (2002).
7. S. C. Mateer, A. E. McDaniel, V. Nicolas, G. M. Habermacher, M. J. Lin, D. A. Cromer, M. E. King and G. S. Bloom, J. Biol. Chem., 277(14), 12324-12333 (2002).
8. A. R. Rhoads and F. Friedberg, FASEB J., 11(5), 331-340 (1997).
9. M. Bahler and A. Rhoads, FEBS Lett., 513(1), 107-113 (2002).
10. Z. Li and D. B. Sacks, J. Biol. Chem., 278(6), 4347-4352 (2003).
11. H. W. Jeong, Z. Li, M. D. Brown and D. B. Sacks, J. Biol. Chem., 282(28), 20752-20762 (2007).
12. A. Heil, A. R. Nazmi, M. Koltzscher, M. Poeter, J. Austermann, N. Assard, J. Baudier, K. Kaibuchi and V. Gerke, J. Biol. Chem. 286(9), 7227-7238 (2011).
13. S. Pathmanathan, S. F. Elliott, S. McSwiggen, B. Greer, P. Harriott, G. B. Irvine and D. J. Timson, Mol. Cell. Biochem., 318(1-2), 43-51 (2008).
14. D. J. Jang, B. Ban and J. A. Lee, Mols. Cells, in press (2011).