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Pneumocystis carinii BCK1 functions in a mitogen‐activated protein kinase cascade regulating fungal cell‐wall assembly
Author(s) -
Thomas Charles F.,
Vohra Pawan K.,
Park John G.,
Puri Veenu,
Limper Andrew H.,
Kottom Theodore J.
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00730-0
Subject(s) - pneumocystis carinii , map kinase kinase kinase , biology , protein kinase a , mapk cascade , microbiology and biotechnology , mitogen activated protein kinase kinase , kinase , cyclin dependent kinase 2 , virology , human immunodeficiency virus (hiv) , pneumocystis jirovecii
Pneumocystis pneumonia remains the most common AIDS‐defining opportunistic infection in people with HIV. The process by which Pneumocystis carinii constructs its cell wall is not well known, although recent studies reveal that molecules such as β‐1‐3‐glucan synthetase ( GSC1 ) and environmental pH‐responsive genes such as PHR1 are important for cell‐wall integrity. In closely related fungi, a specific mitogen‐activated protein kinase (MAPK) cascade regulates cell‐wall assembly in response to elevated temperature. The upstream mitogen‐activated protein kinase kinase kinase (MAPKKK, or MEKK), BCK1, is an essential component in this pathway for maintaining cell‐wall integrity and preventing fungal cell lysis. We have identified a P. carinii MEKK gene and have expressed it in Saccharomyces cerevisiae to gain insights into its function. The P. carinii MEKK, PCBCK1 , corrects the temperature‐sensitive cell lysis defect of bck1Δ yeast. Further, at elevated temperature PCBCK1 restored the signaling defect in bck1Δ yeast to maintain expression of the temperature‐inducible β‐1‐3‐glucan synthetase gene, FKS2 . PCBCK1 , as a functional kinase, is capable of autophosphorylation and substrate phosphorylation. Since glucan machinery is not present in mammals, a better understanding of this pathway in P. carinii might aid in the development of novel medications which interfere with the integrity of the Pneumocystis cell wall.