Protein Kinase A Operates a Molecular Switch That Governs Yeast Pseudohyphal Differentiation

Abstract

The yeast Saccharomyces cerevisiae undergoes a dimorphic filamentous transition in response to nutrient cues that is affected by both mitogen-activated protein kinase and cyclic AMP-protein kinase A signaling cascades. Here two transcriptional regulators, Flo8 and Sfl1, are shown to be the direct molecular targets of protein kinase A. Flo8 and Sfl1 antagonistically control expression of the cell adhesin Flo11 via a common promoter element. Phosphorylation by the protein kinase A catalytic subunit Tpk2 promotes Flo8 binding and activation of the Flo11 promoter and relieves repression by prohibiting dimerization and DNA binding by Sfl1. Our studies illustrate in molecular detail how protein kinase A combinatorially effects a key developmental switch. Similar mechanisms may operate in pathogenic fungi and more complex multicellular eukaryotic organisms.

We thank Maria Cardenas, Daniel Lew, John McCusker, Robin Wharton, Chris Counter, John Rohde, Miguel Arevalo-Rodriguez, and Christina Hull for advice and discussions; Keri Forrester for technical assistance; Christina Hull, John Rohde, and Robin Wharton for comments on the manuscript; Mike Lorenz and Marjorie Brandriss for strains; Chris Armstrong and Namjin Chung in the Guarente laboratory and Marian Carlson for plasmids; and Tina Wilkins for assistance with preparation of the manuscript.

Joseph Heitman is a Burroughs Wellcome Scholar in Molecular Pathogenic Mycology and an associate investigator of the Howard Hughes Medical Institute.