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cAMP/PKA信号转导途径在白念珠菌白灰转换中的功能作用(英文)

王华峰  黄广华  聂鑫怡  陈江野  
【摘要】:正White-opaque switching is one of the high-frequency switching systems in Candida albicans which is the most frequently isolated opportunistic pathogen of humans.We have identified Wor1(white-opaque regulator 1)as a master regulator of white-opaque switching.Whether Wor1 function is regulated by signaling pathways remains unclear.Sequence analysis showed that Wor1 contains a highly conserved motif in its N-terminal TOS9 domain,64KRWTDG69,which is a putative PKA phosphorylation site.Alanine substitution of T67 destroyed the putative phosphorylation site.This point mutation blocked self-activation of WOR1 transcription and therefore blocked Wor1-promoted white-opaque switching.Physical interaction between Wor1 and PKA catalytic subunits(Tpk1 and Tpk2)was not detected in a yeast two-hybrid system,while genetic interaction between Wor1 and Tpk2 was observed.In MTLa/α cells,Tpk2,but not Tpk1, was required for white-opaque switching activated by Wor1.In MTLa cells,deletion of TPK2 delayed transcriptional self-activation of Wor1 and impaired white-opaque switching induced by the ectopic expression of WOR1.These results suggested that Wor1 may be a target of Tpk2 and cAMP/PKA pathway may be involved in regulation of white-opaque switching.

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