[Molecular biology of prostaglandin receptor and L-histidine decarboxylase].
This review summarizes our studies on the molecular biology of prostaglandin (PG) receptors and L-histidine decarboxylase (HDC). Regarding PG receptors, we have cloned five basic PG receptors (DP, EP, FP, IP, TP) and four EP subtypes (EP1-EP4). The PG receptors are divided into three families related to signal transduction systems of the receptors; Gs-couple group (IP, DP, EP2 and EP4), Gq-couple group (TP, FP and EP1), and Gi-couple group (EP3 and its isoform). EP3 isoforms having different C-terminal peptides can couple to distinct G proteins (Gi, Gs, Gq). Tissue specific expression of EP subtype mRNAs was observed in various organs. The phenotypic changes of mice deficient in each receptor are; the abnormal labor in FP-deficient mice, the failure of febrile response in EP3-deficient mice, the abnormal closure of ductus arteriosus after birth in EP4-deficient mice, and the impaired inflammatory swelling and pain responses in IP-deficient mice. Regarding HDC, we have purified mouse HDC from mastocytoma cells, which is a dimer of 53 kDa subunit, and then cloned its cDNA. The size of a cDNA-deduced HDC is 74 kDa. In the rat mast cell line, the endogenous 74 kDa form of HDC was translated in the cytosol and then translocated to the ER, where it was post-translationally processed to the 53 kDa form. On the other hand, the cytosolic 74 kDa form was rapidly degraded by an ATP/ubiquitin-dependent proteasome system. The 74 kDa form without on N-terminal signal sequence is inserted into the ER membrane with a C-terminal segment.
Ichikawa
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Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
D000595:Amino Acid Sequence; D000818:Animals; D006632:Histamine / Q000096:biosynthesis; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D051381:Rats; D011982:Receptors, Prostaglandin / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic
D011982:Receptors, Prostaglandin; D006632:Histamine; D006640:Histidine Decarboxylase