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Published 23 May 2005. doi:10.1083/jcb.200411034
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 4, 657-667
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Junctional membrane inositol 1,4,5-trisphosphate receptor complex coordinates sensitization of the silent EGF-induced Ca2+ signaling

Eun-Mi Hur1,2, Yong-Soo Park1,2, Yang Hoon Huh3,4, Seung Hyun Yoo3,4, Kyung-Chul Woo1,2, Bo-Hwa Choi1,2, and Kyong-Tai Kim1,2

1 National Research Laboratory of Molecular Neurophysiology, Pohang University of Science and Technology, Hyo-ja dong, San31, Pohang, 790-784, South Korea
2 Department of Life Science, Pohang University of Science and Technology, Hyo-ja dong, San31, Pohang, 790-784, South Korea
3 National Creative Research Initiative Center for Secretory Granule Research, Inha University College of Medicine, Jung Gu, Incheon 400-712, South Korea
4 Department of Biochemistry, Inha University College of Medicine, Jung Gu, Incheon 400-712, South Korea

Correspondence to Kyong-Tai Kim: ktk{at}postech.ac.kr

Ca2+ is a highly versatile intracellular signal that regulates many different cellular processes, and cells have developed mechanisms to have exquisite control over Ca2+ signaling. Epidermal growth factor (EGF), which fails to mobilize intracellular Ca2+ when administrated alone, becomes capable of evoking [Ca2+]i increase and exocytosis after bradykinin (BK) stimulation in chromaffin cells. Here, we provide evidence that this sensitization process is coordinated by a macromolecular signaling complex comprised of inositol 1,4,5-trisphosphate receptor type I (IP3R1), cAMP-dependent protein kinase (PKA), EGF receptor (EGFR), and an A-kinase anchoring protein, yotiao. The IP3R complex functions as a focal point to promote Ca2+ release in two ways: (1) it facilitates PKA-dependent phosphorylation of IP3R1 in response to BK-induced elevation of cAMP, and (2) it couples the plasmalemmal EGFR with IP3R1 at the Ca2+ store located juxtaposed to the plasma membrane. Our study illustrates how the junctional membrane IP3R complex connects different signaling pathways to define the fidelity and specificity of Ca2+ signaling.

Abbreviations used in this paper: 2APB, 2-aminoethyl diphenylborate; AKAP, A-kinase anchoring protein; AKAP-IS, AKAP-in silico; BK, bradykinin; DRM, detergent-resistant membrane; EGFR, EGF receptor; IP3R, inositol 1,4,5-trisphosphate receptor; IP3R1, IP3R type 1; NMDA, N-methyl-D-aspartic acid; PKA, cAMP-dependent protein kinase; PM, plasma membrane.


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