CAMP and PKA Signaling

Heterotrimeric G proteins, consisting of the a, p, and y subunits, are primary components of many signal transduction cascades and they, and the signal transduction pathways, are conserved across many different organisms. In Cn, the PKA pathway that regulates cyclic AMP (cAMP) is an example of a signaling pathway involving G proteins that is important for fungal development and virulence (Pukkila-Worley & Alspaugh, 2004). The PKA pathway is activated during nutrient deprivation via a 7-transmembrane domain G protein-coupled receptor (Gpr4) that senses amino acids (methionine) (Xue et al., 2006). Once methionine binds Gpr4, the G proteins are activated and the a subunit (Gpal, Alspaugh et al., 1997) is released from the GPy dimer (D'Souza & Heitman, 2001). In Cn, the Gp subunit is encoded by the Gib2 gene while there are two Gy subunits encoded by the genes Gpg1/2 (Palmer et al., 2006). Gpa1 in combination with the adenylyl cyclase associated protein

(Aca1, Bahn et al., 2004) can bind to the enzyme adenylyl cyclase (Cac1) inducing it to produce cAMP (Alspaugh et al., 2002). cAMP levels are negatively regulated by the phosphodiesterase Pde1 (and possibly by Pde2) (Hicks et al., 2005).

One of the primary targets of cAMP is PKA, which is a tetrameric protein composed of dimeric regulatory subunits (Pkr1) and two monomelic catalytic subunits (Pka1/2) (D'Souza et al., 2001). Increased levels of cAMP result in the release of the regulatory subunits and activation of the kinase. This results in the phosphorylation of downstream targets of the signaling cascade by Pka1/2 (Pukkila-Worley & Alspaugh, 2004) ultimately leading to transcription of genes involved in capsule biosynthesis (Cramer et al., 2006) and melanin production (Pukkila-Worley et al., 2005).

Because strains deficient in PKA are sterile (D'Souza et al., 2001), there is thought to be cross talk between the MAPK and PKA pathways. Thus, one hypothesis is that for Cn to undergo mating, both pathways are needed: the PKA pathway signals nutrient deprivation while the MAPK pathway signals the presence of an appropriate mating partner (Pukkila-Worley & Alspaugh, 2004).

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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