Interactions between the juxtamembrane domain of the EGFR and calmodulin measured by surface plasmon resonance
2002 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 14, no 12, 1005-1013 p.Article in journal (Refereed) Published
One early response to epidermal growth factor receptor (EGFR) activation is an increase in intracellular calcium. We have used surface plasmon resonance (SPR) to study real-time interactions between the intracellular juxtamembrane (JM) region of EGFR and calmodulin. The EGFR-JM (Met644-Phe688) was expressed as a GST fusion protein and immobilised on a sensor chip surface. Calmodulin specifically interacts with EGFR-JM in a calcium-dependent manner with a high on and high off rate. Chemical modification of EGFR-JM by using arginine-selective phenylglyoxal or deletion of the basic segment Arg645-Arg657 inhibits the interaction. Phosphorylation of EGFR-JM by protein kinase C (PKC) or glutamate substitution of Thr654 inhibits the interaction, suggesting that PKC phosphorylation electrostatically interferes with calmodulin binding to basic arginine residues. Calmodulin binding was also inhibited by suramin. Our results suggest that EGFR-JM is essential for epidermal growth factor (EGF)-mediated calcium-calmodulin signalling and for signal integration between other signalling pathways.
Place, publisher, year, edition, pages
2002. Vol. 14, no 12, 1005-1013 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-27056DOI: 10.1016/S0898-6568(02)00034-7Local ID: 11702OAI: oai:DiVA.org:liu-27056DiVA: diva2:247607