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抗酸化性物質であるヘム結合性蛋白HBP23はABLキナーゼ活性を抑制する：丸義朗¹、阿部靖子²、西野武士²、渋谷正史¹（¹東大医科研　細胞遺伝、²日本医科大　第一生化）

Thiol-specific antioxidant HBP23 inhibits the ABL kinase activity : Yoshiro MARU¹, Yasuko ABE², Takeshi NISHINO², Masabumi SHIBUYA¹ (¹Dept. of Genetics, Inst. Med. Sci., Univ. Tokyo, ²Dept. of Biochem., Nippon Med. School)

The ABL tyrosine kinase is involved in cell cycle, DNA repair, and in the formation of the human leukemia oncogene BCR-ABL. The idea that the SH3 domain negatively regulates ABL is based on the fact that retrovirally activated v-ABL lacks the SH3 domain and it prompted many investigators to find SH3-binding proteins including Abi-2, AAP1, PAG and so forth.
Among these PAG, a human gene identified by the yeast two-hybrid system, was claimed to be a physiological ABL inhibitor because the protein was the only one that has been documented to inhibit the ABL autophosphorylation activity when transiently co-overexpressed with ABL in 293T cells. Here we report the interaction between ABL and a heme-binding protein sized 23 KD (HBP23) of rat origin which is highly homologous to PAG. The purified HBP23 could bind to the purified ABL SH3 domain fused to glutathione S-transferase (GST-SH3) but not to GST-SH2 or GST alone. As judged by the in vitro kinase assay, the purified HBP23 inhibited the autophosphorylation activity of BCR-ABL which contains the SH3 domain but not that of v-ABL that lacks it. Given that tyrosine phosphorylation of HBP23 was prominently observed with v-ABL, the interaction between those two proteins are not soly dependent on the ABL SH3 domain. In order to examine if constitutive binding of HBP23 to the ABL SH3 domain is responsible for the tight down-regulation of the ABL kinase activity in vivo, we tried to detect HBP23 proteins in anti-ABL immunoprecipitates from rat endothelial cells that expressed HBP23 with the endogenous ABL or with BCR-ABL but in vain. We suppose that HBP23 can certainly inhibit the ABL kinase activity partly utilizing the ABL SH3 domain but that it may not be a physiologically dominant inhibitor.