Defining the human targets of phorbol ester and diacylglycerol.
Phorbol esters (PEs) and their derivatives are potent tumor-promoting agents. The best known receptors for these substances are the novel and classical isotypes of protein kinase C (PKC), which bind PE and the physiological second messenger diacylglycerol (DAG) by cysteine-rich domains, the C1 domains. However, PKC is not the sole receptor of PE, a concept that has been largely ignored in the past. PE (in addition to DAG) also targets C1-containing receptors unrelated to PKC. In order to get a better insight into DAG/PE-mediated signaling and the pathways involved, it is necessary to first determine all ligand-interacting proteins. Employing various sources of data, 66 different C1-containing human proteins are presented and predictions of their DAG/PE-binding potential are attempted. Defining the entire set of key mediators for the physiological DAG responses and for PE-induced tumorigenesis may aid our understanding of signal integration and can also help to design new strategies for therapeutic cancer intervention.
Geiger
Markus
M
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregistr 3, A-6020 Innsbruck, Austria. markus.geiger@uibk.ac.at
Wrulich
Oliver A
OA
Jenny
Marcel
M
Schwaiger
Wolfgang
W
Grunicke
Hans H
HH
Uberall
Florian
F
D000595:Amino Acid Sequence; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D030562:Databases, Protein; D004075:Diglycerides / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment
D002273:Carcinogens; D004075:Diglycerides; D010703:Phorbol Esters; D011506:Proteins