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Gene Review

PKH1  -  Pkh1p

Saccharomyces cerevisiae S288c

Synonyms: 3-phosphoinositide-dependent protein kinase 1, Serine/threonine-protein kinase PKH1, YDR490C
 
 
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Disease relevance of PKH1

  • The translation defect during heat stress in lcb1-100 was due at least partially to a reduced function of the sphingoid base-activated PKH1/2 protein kinases [1].
 

High impact information on PKH1

  • The threonine in Ypk1 that is phosphorylated by Pkh1 is required for efficient endocytosis, and pkh mutant cells are defective in alpha-factor internalization and fluid-phase endocytosis [2].
  • Pkh1p and Pkh2p have an overlapping function because only a mutant with impaired function of both kinases is defective for endocytosis [3].
  • The Pkc1p kinase that is phosphorylated by Pkh1/2p kinases and plays a role in endocytosis was identified as one of the downstream effectors of this signaling cascade [3].
  • Pkh1/2p kinases are activated in vitro by nanomolar concentrations of sphingoid base [3].
  • These results suggest that Pkh1/2p kinases are part of a sphingoid base-mediated signaling pathway that is required for the internalization step of endocytosis [3].
 

Biological context of PKH1

 

Anatomical context of PKH1

  • The Pkh1 protein kinase of Saccharomyces cerevisiae, a homolog of the mammalian 3-phosphoinositide-dependent kinase (PDK1), regulates downstream AGC-type protein kinases including Ypk1/2 and Pkc1, which control cell wall integrity, growth, and other processes [6].
 

Associations of PKH1 with chemical compounds

  • Saccharomyces cerevisiae Pkh1 and Pkh2 are functionally redundant homologs of mammalian protein kinase, phosphoinositide-dependent protein kinase-1 [5].
  • Taking both the inability to produce PI-3,4, 5-triphosphate and PI-3,4-bisphosphate and the lack of a PH domain in the yeast homologue of PDK1, the Pkh1 protein, into account, these findings further suggest that yeast may use sphingolipids instead of inositol phospholipids as lipid mediators [7].
 

Enzymatic interactions of PKH1

 

Regulatory relationships of PKH1

 

Other interactions of PKH1

  • Pil1p and Lsp1p are thus the first proteins identified as regulators of Pkh1/2p [8].
  • We further demonstrate that Slm proteins are regulated by a phosphorylation/dephosphorylation cycle involving the sphingolipid-activated protein kinases Pkh1 and Pkh2 and the calcium/calmodulin-dependent protein phosphatase calcineurin [9].
  • Greatest stimulation of Ypk1/2 phosphorylation and activity are achieved by inclusion of both PHS and Pkh1 in an in vitro kinase reaction [6].

References

  1. Sphingoid base is required for translation initiation during heat stress in Saccharomyces cerevisiae. Meier, K.D., Deloche, O., Kajiwara, K., Funato, K., Riezman, H. Mol. Biol. Cell (2006) [Pubmed]
  2. The conserved Pkh-Ypk kinase cascade is required for endocytosis in yeast. deHart, A.K., Schnell, J.D., Allen, D.A., Hicke, L. J. Cell Biol. (2002) [Pubmed]
  3. Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast. Friant, S., Lombardi, R., Schmelzle, T., Hall, M.N., Riezman, H. EMBO J. (2001) [Pubmed]
  4. Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Casamayor, A., Torrance, P.D., Kobayashi, T., Thorner, J., Alessi, D.R. Curr. Biol. (1999) [Pubmed]
  5. Pkh1 and pkh2 differentially phosphorylate and activate ypk1 and ykr2 and define protein kinase modules required for maintenance of cell wall integrity. Roelants, F.M., Torrance, P.D., Bezman, N., Thorner, J. Mol. Biol. Cell (2002) [Pubmed]
  6. The sphingoid long chain base phytosphingosine activates AGC-type protein kinases in Saccharomyces cerevisiae including Ypk1, Ypk2, and Sch9. Liu, K., Zhang, X., Lester, R.L., Dickson, R.C. J. Biol. Chem. (2005) [Pubmed]
  7. Sli2 (Ypk1), a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. Sun, Y., Taniguchi, R., Tanoue, D., Yamaji, T., Takematsu, H., Mori, K., Fujita, T., Kawasaki, T., Kozutsumi, Y. Mol. Cell. Biol. (2000) [Pubmed]
  8. Pil1p and Lsp1p negatively regulate the 3-phosphoinositide-dependent protein kinase-like kinase Pkh1p and downstream signaling pathways Pkc1p and Ypk1p. Zhang, X., Lester, R.L., Dickson, R.C. J. Biol. Chem. (2004) [Pubmed]
  9. The Yeast PH Domain Proteins Slm1 and Slm2 Are Targets of Sphingolipid Signaling during the Response to Heat Stress. Daquinag, A., Fadri, M., Jung, S.Y., Qin, J., Kunz, J. Mol. Cell. Biol. (2007) [Pubmed]
 
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