title: Cloning and characterization of human type 2 and type 3 inositol 1,4,5-trisphosphate receptors.
abstract: We have cloned cDNAs coding for human type 2 and type 3 and part of type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs). The complete nucleotide sequences for type 2 and type 3 receptors were determined and the pharmacological properties of the latter were characterized. Human type 2 and type 3 IP3Rs are 2701 amino acids and 2671 amino acids long, respectively, and have significant sequence homologies as well as structural similarities including the six membrane-spanning regions near the C-termini when compared with the rat or mouse counterpart. COS-7 cells transfected with human type 3 IP3R showed characteristic inositol 1,4,5-trisphosphate (IP3)-binding properties with Kd values of 28.8 nM. The order of potency of competition with IP3 was Ins(1,4,5)P3 (IP3) > Ins(2,4,5)P3 > Ins(1,3,4,5)P4 > Ins(1,2,3,4,5,6)P6. Type 2 and type 3 IP3Rs were mapped to human chromosomes 12p11 and 6p21, respectively, by in situ hybridization. cDNA cloning of the human IP3Rs allowed us to identify the types of the receptor expressed in various human hematopoietic and lymphoma cell lines. The type 3 receptor was present in all of cell lines tested, while the type 1 or 2 receptor was expressed in only particular cell types. The differential expression of the IP3R types could confer the cell-specific regulation on the IP3/Ca2+ signalling.
authors.affiliation: Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto-Hino
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: K
authors.initials: K
authors.lastname: Hikichi
authors.forename: M G
authors.initials: MG
authors.lastname: Mattei
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
authors.forename: S
authors.initials: S
authors.lastname: Sekine
authors.forename: K
authors.initials: K
authors.lastname: Sakurada
authors.forename: A
authors.initials: A
authors.lastname: Miyawaki
authors.forename: T
authors.initials: T
authors.lastname: Furuichi
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015220:Calcium Channels / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D015220:Calcium Channels; D018076:DNA, Complementary; C506926:ITPR1 protein, human; C506927:ITPR2 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate