Disease relevance of YPK1

• When overexpressed, a catalytically active C-terminal fragment (kinase domain) of Ypk1 was growth inhibitory; loss of Pkh1 (but not Pkh2) alleviated toxicity [1].

High impact information on YPK1

• 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].
• The kinase activity of Ypk1 is required for receptor endocytosis because mutations in two residues important for its catalytic activity cause a severe defect in alpha-factor internalization [2].
• Ypk1 is required for both receptor-mediated and fluid-phase endocytosis, and is not necessary for receptor phosphorylation or ubiquitination [2].
• In a screen to detect proteins involved in ubiquitin-dependent receptor internalization, we identified the sphingoid base-regulated serine-threonine kinase Ypk1 [2].
• One of these genes, SLI2, is synonymous with YPK1, which encodes a serine/threonine kinase [3].

Biological context of YPK1

• Mapping of DBR1 and YPK1 suggests a major revision of the genetic map of the left arm of Saccharomyces cerevisiae Chromosome XI [4].
• In our previous study, YPK1/SLI2 was identified as one of multicopy suppressor genes for ISP-1 in yeast [5].
• On a sli1-null background, the increase in resistance to ISP-1 induced by YPK1 gene transfection was almost abolished [6].
• Pkh1 activated purified Ypk1 by phosphorylating the equivalent residue (Thr504) and was required for maximal Ypk1 phosphorylation in vivo [7].
• A pair of putative protein kinase genes (YPK1 and YPK2) is required for cell growth in Saccharomyces cerevisiae [8].

Anatomical context of YPK1

• The major voltage-dependent ion channel in the plasma membrane of Saccharomyces cerevisiae, a conspicuous outwardly rectifying K+ channel, was first dubbed YPK1 and later renamed according to its registered gene names (DUK1, TOK1) [9].
• 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 [10].

Associations of YPK1 with chemical compounds

• In a previous study, we cloned yeast multicopy suppressor genes for ISP-1, and one of these, YPK1/SLI2, was shown to encode a serine/threonine kinase which is a yeast homologue of mammalian SGK1 (serum/glucocorticoid-regulated kinase 1) [6].
• In addition, Ypk1 as well as eIF4G protein levels were rapidly depleted upon nitrogen starvation, but not during glucose starvation, even though both conditions inhibit translation initiation [11].

Regulatory relationships of YPK1

• Phytosphingosine (PHS), a sphingoid long chain base, is hypothesized to be a lipid activator of Pkh1 and thereby controls the activity of Ypk1/2 [10].

Other interactions of YPK1

• A protein kinase-encoding gene, pkt1, from Trichoderma reesei, homologous to the yeast YPK1 and YPK2 (YKR2) genes [12].
• Greatest stimulation of Ypk1/2 phosphorylation and activity are achieved by inclusion of both PHS and Pkh1 in an in vitro kinase reaction [10].
• Here, genetic and biochemical methods have been used to investigate the physiological consequences of phosphorylation at the PDK1 and PDK2 sites of Ypk1, Pkc1 and Sch9 [13].

Analytical, diagnostic and therapeutic context of YPK1

• Sequence analysis revealed that MCK1 encodes a protein kinase homolog identical to YPK1, a phosphotyrosyl protein with demonstrated protein kinase activity [14].

References