title: A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells.
abstract: 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.
authors.affiliation: Center for Biomedical Research, 1301 Punchbowl St., University Tower 8, Honolulu, HI 96813, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stokes
authors.forename: Lori M N
authors.initials: LM
authors.lastname: Shimoda
authors.forename: Murielle
authors.initials: M
authors.lastname: Koblan-Huberson
authors.forename: Chaker N
authors.initials: CN
authors.lastname: Adra
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002412:Cations; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D050916:TRPV Cation Channels; D013696:Temperature; D013997:Time Factors
chemical_list: C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters; C489272:Abcd3 protein, rat; D015220:Calcium Channels; D002412:Cations; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D012701:Serotonin; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium