Junctional membrane inositol 1,4,5-trisphosphate receptor complex coordinates sensitization of the silent EGF-induced Ca2+ signaling.
Ca(2+) is a highly versatile intracellular signal that regulates many different cellular processes, and cells have developed mechanisms to have exquisite control over Ca(2+) signaling. Epidermal growth factor (EGF), which fails to mobilize intracellular Ca(2+) when administrated alone, becomes capable of evoking [Ca(2+)](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 (IP(3)R1), cAMP-dependent protein kinase (PKA), EGF receptor (EGFR), and an A-kinase anchoring protein, yotiao. The IP(3)R complex functions as a focal point to promote Ca(2+) release in two ways: (1) it facilitates PKA-dependent phosphorylation of IP(3)R1 in response to BK-induced elevation of cAMP, and (2) it couples the plasmalemmal EGFR with IP(3)R1 at the Ca(2+) store located juxtaposed to the plasma membrane. Our study illustrates how the junctional membrane IP(3)R complex connects different signaling pathways to define the fidelity and specificity of Ca(2+) signaling.
Hur
Eun-Mi
EM
National Research Laboratory of Molecular Neurophysiology, Pohang University of Science and Technology, Hyo-ja dong, San31, Pohang, 790-784, South Korea.
Park
Yong-Soo
YS
Huh
Yang Hoon
YH
Yoo
Seung Hyun
SH
Woo
Kyung-Chul
KC
Choi
Bo-Hwa
BH
Kim
Kyong-Tai
KT
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000187:drug effects / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007365:Intercellular Junctions / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C486537:Akap9 protein, rat; D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; C488910:Itpr1 protein, rat; D008562:Membrane Glycoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; C483803:Egfr protein, rat; D066246:ErbB Receptors; D017868:Cyclic AMP-Dependent Protein Kinases; D001920:Bradykinin; D002118:Calcium