Ward M P, Gimeno C J, Fink G R, Garrett S
Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Mol Cell Biol. 1995 Dec;15(12):6854-63. doi: 10.1128/MCB.15.12.6854.
Yeast cyclic AMP (cAMP)-dependent protein kinase (PKA) activity is essential for growth and cell cycle progression. Dependence on PKA function can be partially relieved by overexpression of a gene, SOK2, whose product has significant homology with several fungal transcription factors (StuA from Aspergillus nidulans and Phd1 from Saccharomyces cerevisiae) that are associated with cellular differentiation and development. Deletion of SOK2 is not lethal but exacerbates the growth defect of strains compromised for PKA activity. Alterations in Sok2 protein production also affect the expression of genes involved in several other PKA-regulated processes, including glycogen accumulation (GAC1) and heat shock resistance (SSA3). These results suggest SOK2 plays a general regulatory role in the PKA signal transduction pathway. Expression of the PKA catalytic subunit genes is unaltered by deletion or overexpression of SOK2. Because homozygous sok2/sok2 diploid strains form pseudohyphae at an accelerated rate, the Sok2 protein may inhibit the switch from unicellular to filamentous growth, a process that is dependent on cAMP. Thus, the product of SOK2 may act downstream of PKA to regulate the expression of genes important in growth and development.
酵母环磷酸腺苷(cAMP)依赖性蛋白激酶(PKA)活性对于生长和细胞周期进程至关重要。通过基因SOK2的过表达可部分缓解对PKA功能的依赖性,该基因的产物与几种与细胞分化和发育相关的真菌转录因子(构巢曲霉的StuA和酿酒酵母的Phd1)具有显著同源性。SOK2的缺失并不致命,但会加剧PKA活性受损菌株的生长缺陷。Sok2蛋白产量的改变也会影响参与其他几种PKA调节过程的基因的表达,包括糖原积累(GAC1)和耐热性(SSA3)。这些结果表明SOK2在PKA信号转导途径中发挥着一般调节作用。PKA催化亚基基因的表达不受SOK2缺失或过表达的影响。由于纯合的sok2/sok2二倍体菌株以加速速率形成假菌丝,Sok2蛋白可能会抑制从单细胞生长到丝状生长的转变,这一过程依赖于cAMP。因此,SOK2的产物可能在PKA下游发挥作用,以调节生长和发育中重要基因的表达。