Schizosaccharomyces pombe Git1 is a C2-domain protein required for glucose activation of adenylate cyclase

Schizosaccharomyces pombe senses environmental glucose through a cAMP-signaling pathway, activating cAMP-dependent protein kinase A (PKA). This requires nine git genes (git=glucose insensitive transcription) that encode adenylate cyclase, the PKA catalytic subunit and seven "upstream" proteins required for glucose-triggered adenylate cyclase activation, including three heterotrimeric G protein subunits and its associated receptor. We describe here the cloning and characterization of the git1+ gene. Git1 is distantly related to a small group of uncharacterized fungal proteins, including a second S. pombe protein that is not functionally redundant with Git1, as well as to members of the UNC-13/Munc13 protein family. Mutations in git1+ demonstrate functional roles for the two most highly conserved regions of the protein, the C2 domain and the MHD2 Munc homology domain. Cells lacking Git1 are viable, but display phenotypes associated with cAMP signaling defects, even in strains expressing a mutationally-activated G? subunit, which activates adenylate cyclase. These cells possess reduced basal cAMP levels and fail to mount a cAMP response to glucose. In addition, Git1 and adenylate cyclase physically interact and partially co-localize in the cell. Thus, Git1 is a critical component of the S. pombe glucose/cAMP pathway.

Key Words: Git1, Schizosaccharomyces pombe, adenylate cyclase, cAMP, glucose

This article has been cited by other articles:

				M. A. Alaamery and C. S. Hoffman Schizosaccharomyces pombe Hsp90/Git10 Is Required for Glucose/cAMP Signaling Genetics, April 1, 2008; 178(4): 1927 - 1936. [Abstract] [Full Text] [PDF]

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