Nocero M, Isshiki T, Yamamoto M, Hoffman C S
Department of Biology, Boston College, Chestnut Hill, Massachusetts 02167.
Genetics. 1994 Sep;138(1):39-45. doi: 10.1093/genetics/138.1.39.
In the fission yeast Schizosaccharomyces pombe, genetic studies have identified genes that are required for glucose repression of fbp1 transcription. The git2 gene, also known as cyr1, encodes adenylate cyclase. Adenylate cyclase converts ATP into the second messenger cAMP as part of many eukaryotic signal transduction pathways. The git1, git3, git5, git7, git8 and git10 genes act upstream of adenylate cyclase, presumably encoding an adenylate cyclase activation pathway. In mammalian cells, adenylate cyclase enzymatic activity is regulated by heterotrimeric guanine nucleotide-binding proteins (G proteins). In the budding yeast Saccharomyces cerevisiae, adenylate cyclase enzymatic activity is regulated by monomeric, guanine nucleotide-binding Ras proteins. We show here that git8 is identical to the gpa2 gene that encodes a protein homologous to the alpha subunit of a G protein. Mutations in two additional genes, git3 and git5 are suppressed by gpa2+ in high copy number. Furthermore, a mutation in either git3 or git5 has an additive effect in strains deleted for gpa2 (git8), as it significantly increases expression of an fbp1-lacZ reporter gene. Therefore, git3 and git5 appear to act either in concert with or independently from gpa2 (git8) to regulate adenylate cyclase activity.
在裂殖酵母粟酒裂殖酵母中，遗传学研究已鉴定出fbp1转录的葡萄糖抑制所需的基因。git2基因，也称为cyr1，编码腺苷酸环化酶。腺苷酸环化酶将ATP转化为第二信使cAMP，这是许多真核信号转导途径的一部分。git1、git3、git5、git7、git8和git10基因在腺苷酸环化酶上游起作用，推测编码一种腺苷酸环化酶激活途径。在哺乳动物细胞中，腺苷酸环化酶的酶活性由异三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）调节。在芽殖酵母酿酒酵母中，腺苷酸环化酶的酶活性由单体鸟嘌呤核苷酸结合Ras蛋白调节。我们在此表明，git8与gpa2基因相同，该基因编码一种与G蛋白α亚基同源的蛋白质。另外两个基因git3和git5中的突变在高拷贝数的gpa2+存在时被抑制。此外，git3或git5中的一个突变在缺失gpa2（git8）的菌株中具有累加效应，因为它会显著增加fbp1-lacZ报告基因的表达。因此，git3和git5似乎与gpa2（git8）协同作用或独立于gpa2（git8）来调节腺苷酸环化酶活性。
