Thromboxane A2-induced signal transduction is negatively regulated by KIAA1005 that directly interacts with thromboxane A2 receptor.
Thromboxane A(2) (TXA(2)), a potent inducer of platelet aggregation and smooth muscle contraction, exerts its action through TXA(2) receptor (TP). There are two alternative splicing variants of TP, TP alpha and TP beta. To clarify the signal transduction of TP pathway, we searched for putative TP binding proteins using a yeast two-hybrid system with the C-terminal region of TP alpha or TP beta as bait. We found KIAA1005 as a novel interacting protein of the TP alpha and TP beta C-terminal region (TP interacting protein, TPIP). KIAA1005/TPIP was co-immunoprecipitated with TP alpha or TP beta in HEK293 cells expressing myc-KIAA1005/TPIP and FLAG-TP isoforms. Expression analysis showed a ubiquitous expression pattern of KIAA1005/TPIP mRNA, including prominent expression in the thymus. Furthermore, TP-mediated phosphoinositide hydrolysis, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and interleukin-6 production were reduced by the expression of KIAA1005/TPIP. The expression of KIAA1005/TPIP decreased cell-surface TP alpha and TP beta levels. Thus, we show for the first time that KIAA1005/TPIP is a novel TP interacting protein that regulates TP-mediated signal transduction negatively.
Tokue
Shin-ichi
S
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Sasaki
Masako
M
Nakahata
Norimichi
N
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013928:Thromboxane A2 / Q000494:pharmacology*
D048868:Adaptor Proteins, Signal Transducing; D015850:Interleukin-6; D010716:Phosphatidylinositols; D012333:RNA, Messenger; C532826:RPGRIP1L protein, human; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D048052:Mitogen-Activated Protein Kinase 3