Ras2

Ras2 is a Saccharomyces cerevisiae guanine nucleotide-binding protein (encoded by the RAS2 gene) which becomes activated by binding GTP when glucose is present in the environment. It affects growth regulation and starvation response.[1]

Modifications

Ras2 becomes post-translationally modified in two ways, both being necessary for its activity: Upon activation, palmitoylation at its C terminus takes place and causes attachment from the cytoplasm to the plasma membrane. Farnesylation allows for efficient interaction with the downstream adenylate cyclase Cyr1p.[2] In wild-type yeast deactivated Ras2 is transported to and degraded in the vacuole, a process for which Whi2 is essential. Disturbing this process leads to Ras2 accumulation at the mitochondrial membrane, a behavior that was not observed before.[3]

Ras2-cAMP-PKA pathway

When activating the adenylate cyclase, Ras2 indirectly raises the cellular cAMP levels, thereby activating the PKA, by which in turn it is downregulated.[4]

Downstream effects

In a probably indirect manner via the above PKA regulation, Ras2 has a suppressing effect on the yeast general stress response transcription factor Msn2.[5]

Active Ras2 was also found in the nucleus, the reason is currently unknown.

References

  1. "RAS2/YNL098C Protein Information". Saccharomyces Genome Database. Retrieved 4 January 2012.
  2. Bhattacharya, Sharmila; Chen, Li; Broach, James R.; Powers, Scott (1995). "Ras Membrane Targeting is Essential for Glucose Signaling but not for Viability in Yeast". Proceedings of the National Academy of Sciences. 92 (7): 2984–8. Bibcode:1995PNAS...92.2984B. doi:10.1073/pnas.92.7.2984. JSTOR 2367245. PMC 42343. PMID 7708760.
  3. Leadsham, Jane E.; Miller, Katherine; Ayscough, Kathryn R.; Colombo, Sonia; Martegani, Enzo; Sudbery, Pete; Gourlay, Campbell W. (2009). "Whi2 links nutritional sensing to actin-dependent Ras-cAMP-PKA regulation and apoptosis in yeast". Journal of Cell Science. 122 (5): 706–15. doi:10.1242/jcs.042424. PMC 2720921. PMID 19208759.
  4. Dong, Jian; Bai, Xiaojia (2011). "The membrane localization of Ras2 and the association between Cdc25p and Ras2-GTP are regulated by protein kinase A (PKA) in the yeast Saccharomyces cerevisiae". FEBS Letters. 585 (8): 1127–34. doi:10.1016/j.febslet.2011.03.057. PMID 21457714. S2CID 27110.
  5. Sadeh, Amit; Movshovich, Natalia; Volokh, Misha; Gheber, Larisa; Aharoni, Amir (2011). "Fine-tuning of the Msn2/4-mediated yeast stress responses as revealed by systematic deletion of Msn2/4 partners". Molecular Biology of the Cell. 22 (17): 3127–38. doi:10.1091/mbc.E10-12-1007. PMC 3164460. PMID 21757539.
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