Kinase Subfamily PKC-fun
Kinase Classification: Group AGC: Family PKC: Subfamily PKC-fun
PKC-fun is a PKC subfamily found almost uniquely in fungi, with a distinct domain architecture and a role in responding to cell-wall stress in a fungal-specific pathway.
Evolution
PKC-fun is found in all major classes of fungi, but nowhere else. While classified as a PKC, its structure and function are more closely related to the PKN family, which also contains HR1 domains and is activated by the Rho small GTPase.
Domain Structure
It has a characteristic N-terminal array of three HR1 domains, followed by a C2 domain, two C1 domains, and a protein kinase domain. The domain sequences are divergent and not always captured by sequence profile models.
Functions
The subfamily is best studied in the single Saccharomyces homolog, Pkc1 [1]. Cell wall stress activates the Rho1 GTPase, which in turn activates Pkc1 by binding to the HR1 domains and enabling phosphorylation of Pkc1 by the PDK1 homologs Pkh1/2. Pkc1 then activates a MAPK cascade by phosphorylating the MEKK, BKC1 (Ste11 family), which then phosphorylates and activates MKK1 and MKK2, and in turn, activates Slt2. These genes are part of the Cell Wall Integrity (CWI) pathway, which is unique to and conserved across fungi [2]. Ypk1 is also activated by TORC2 signaling [3], by phosphorylation on the C-terminal tail.
References
- Heinisch JJ, Lorberg A, Schmitz HP, and Jacoby JJ. The protein kinase C-mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae. Mol Microbiol. 1999 May;32(4):671-80. DOI:10.1046/j.1365-2958.1999.01375.x |
- Dichtl K, Samantaray S, and Wagener J. Cell wall integrity signalling in human pathogenic fungi. Cell Microbiol. 2016 Sep;18(9):1228-38. DOI:10.1111/cmi.12612 |
- Roelants FM, Leskoske KL, Martinez Marshall MN, Locke MN, and Thorner J. The TORC2-Dependent Signaling Network in the Yeast Saccharomyces cerevisiae. Biomolecules. 2017 Sep 5;7(3). DOI:10.3390/biom7030066 |
