The Journal of Experimental Medicine
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Published online 12 July 2004 doi:10.1084/jem.20032082
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 2, 137-147
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A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells

Alexander J. Stokes1, Lori M.N. Shimoda1, Murielle Koblan-Huberson1, Chaker N. Adra2, and Helen Turner1,3

1 Center for Biomedical Research at the Queen's Medical Center, Honolulu, HI 96813
2 Beth Israel Deaconess Medical Center, Boston, MA 02215
3 Department of Cell and Molecular Biology, University of Hawaii, Honolulu, HI 96822

Address correspondence to Helen Turner, Center for Biomedical Research, 1301 Punchbowl St., University Tower 8, Honolulu, HI 96813. Phone: (808) 537-7927; Fax: (808) 537-7926; email: hturner{at}queens.org

Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation.

Key Words: calcium channels • inflammation • physical urticaria • transient receptor potential • vanilloid receptor


Abbreviations used in this paper: ACBD, Acyl CoA binding domain protein; AKAP, A kinase adapter protein; BMMC, BM-derived mast cell; PKA, protein kinase A; PKAR, PKA regulatory; PKG, protein kinase G; PU, physical urticaria; TRPV, transient receptor potential (vanilloid); VDAC, voltage-dependent anion channel.


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