Disease relevance of MSS4

• Expression of this cDNA in Escherichia coli produced an active PIP5K [1].

High impact information on MSS4

• The predicted amino acid sequence for the 2.7 kb transcript reported here shows a marked homology to the deduced amino acid sequence of the Saccharomyces cerevisiae MSS4 protein, proposed to function within the phosphoinositide cycle, suggesting a potential role for the human homologue in signal transduction [2].
• MSS4 encodes a phosphatidylinositol-4-phosphate 5-kinase that synthesizes phosphatidylinositol (4,5)-bisphosphate (PI4,5P(2)) [3].
• We characterized a novel multicopy suppressor gene of ISP-1-mediated cell death in yeast, MSS4 [3].
• The phenotypes observed in synaptojanin-deficient cells correlated with accumulation of PtdIns(4,5)P(2), because these effects were rescued by mutations in MSS4 or a mutant form of Sjl2p that harbors only PI 5-phosphatase activity [4].
• Two Saccharomyces cerevisiae genes, MSS4 and FAB1, are homologous to mammalian PtdIns(4)P 5Ks and PtdIns(5)P 4Ks [5].

Biological context of MSS4

• MSS4 is predicted to encode a hydrophilic protein of 779 amino acid residues and is essential for cell growth [6].
• MSS4 has dual substrate specificity in vitro, converting PI(4)P to PI(4, 5)P2 and to a lesser extent PI(3)P to PI(3,4)P2; no activity was detected with PI or PI(5)P as a substrate [7].
• A gene with significant sequence homology to the S. cerevisiae PI4P5K was cloned and designated MSS4 [8].
• The final step in the synthesis of PtdIns(4,5)P2 is the phosphorylation of PtdIns(4)P- by PtdIns(4)P 5-kinase (PIP5K) [1].
• We hypothesize that AtP5K1, like animal and yeast PIP5K, may be involved in the control of cell proliferation [9].

Anatomical context of MSS4

• These results suggest that MSS4 is the major PI(4)P 5-kinase in yeast and provide a link between phosphoinositide metabolism and organization of the actin cytoskeleton in vivo [7].
• The presence of dibasic residues at the C-terminal end of KHD was conserved among mammalian as well as invertebrate PIP5K family members, but not in the type II PIPKs that are not targeted to the plasma membrane, suggesting that the conserved dibasic motif provides a mechanism essential for the proper localization and cellular function of PIP5Ks [10].

Associations of MSS4 with chemical compounds

• Overexpression of the phosphatidylinositol 4-phosphate 5-kinase homolog MSS4 conferred wortmannin resistance, as did deletion of phospholipase C-1 [11].
• These observations support a model for a phosphatidylinositol metabolic cascade involving STT4, MSS4, and phospholipase C-1 and provide evidence that an essential product of this pathway is the lipid phosphatidylinositol 4,5-bisphosphate [11].

Other interactions of MSS4

• Surprisingly, overexpression of PLC1 and MSS4 also suppressed the growth defect of a class B mutant [12].
• Suppression by MSS4 is specific to molecules that contain the Spo20p helical domains [13].
• Based on genetic and biochemical data, we suggest that MSS4 acts downstream of STT4, but in a pathway that does not involve PKC1 [6].

Analytical, diagnostic and therapeutic context of MSS4

• The existence of a PIP5K family of enzymes has been suggested by Western blotting and purification of numerous PIP5Ks from various tissues and cell types [14].
• In cell cultures, overexpression of Type I PIP5-kinase specifically increases PIP(2), whereas overexpression of Type II PI4-kinase can increase both PIP and PIP(2) [15].

References