CWI signaling pathway. Signals are initiated at the plasma membrane (PM) through the cell surface sensors Wsc1, -2, and -3, Mid2, and Mtl1. The extracellular domains of these proteins are highly O-mannosylated. Together with PI4,5P2, which recruits the Rom1/2 GEFs to the plasma membrane, the sensors stimulate nucleotide exchange on Rho1. Relative input of each sensor is indicated by the width of the arrows. Rho1 activates five effectors, including the Pkc1-MAP kinase cascade, the β1,3-glucan synthase (GS), the Bni1 formin protein, the exocyst component Sec3, and the Skn7 transcription factor. Additional regulatory inputs from the Tus1 GEF, the inhibitory Rho1 GAPs, and the Pkh1/2 protein kinases are indicated. Pkh1/2 are activated by phytosphingosine (PHS). The MAP kinase cascade, which is comprised of Bck1, Mkk1/2, and Mpk1, is activated by Pkc1. Several MAP kinase phosphatases downregulate Mpk1. Two transcription factors, Rlm1 and the SBF complex (Swi4/Swi6), are targets of the MAP kinase.