Stt4 PI 4-Kinase Localizes to the Plasma Membrane and Functions in the Pkc1-Mediated MAP Kinase Cascade

Audhya, Anjon; Emr, Scott D.

doi:10.1016/s1534-5807(02)00168-5

Cited by 243 publications

(371 citation statements)

References 56 publications

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“…CHO1 and SFK1 (membrane biogenesis), RTA2, RTA3, and RTA4 (putative flippases), and PLC2, PLC3, and PLB4 (phospholipases), were significantly modulated in both mutants (see Table S2 at http://candida.bri.nrc.ca/papers/myo/). Phospholipases and Sfk1p play an important role in intracellular signaling (6,56). It is intriguing that three independent flippase genes are overexpressed in the mutants.…”

Section: Resultsmentioning

confidence: 99%

Transcript Profiles of Candida albicans Cortical Actin Patch Mutants Reflect Their Cellular Defects: Contribution of the Hog1p and Mkc1p Signaling Pathways

et al. 2006

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In Candida albicans, Myo5p and Sla2p are required for the polarized localization and function of cortical actin patches, for hyphal formation, and for endocytosis. Deletion of either the MYO5 or the SLA2 gene generated a common transcriptional response that involved changes in the transcript levels of cell wall proteinand membrane protein-encoding genes. However, these profiles were distinct from those observed for a mutant with specific deletions of the actin-organizing domains of Myo5p or for wild-type cells treated with cytochalasin A, both of which also generate defects in the organization of cortical actin patches. The profiles observed for the myo5⌬ and sla2⌬ mutants had similarities to those of wild-type cells subjected to an osmotic shock, and the defects in cortical patch function found with myo5⌬ and sla2⌬ mutants, but not cortical actin patch distribution per se, affected sensitivity to various stresses, including heat and osmotic shocks and cell wall damage. Secondary effects coupled with defective endocytosis, such as lack of polarized lipid rafts and associated protein Rvs167-GFP (where GFP is green fluorescent protein) and lack of polarized wall remodeling protein GFP-Gsc1, were also observed for the myo5⌬ and sla2⌬ mutants. The mitogen-activated protein kinases Hog1p and Mkc1p, which mediate signaling in response to osmotic stress and cell wall damage, do not play a major role in regulating the transcript level changes in the myo5⌬ and sla2⌬ mutants. Hog1p was not hyperphosphorylated in the myo5⌬ and sla2⌬ mutants, and the transcript levels of only a subset of genes affected in the myo5⌬ mutant were dependent upon the presence of Hog1p and Mkc1p. However, it appears that Hog1p and Mkc1p play important roles in the myo5⌬ mutant cells because double deletion of myosin I and either Hog1p or Mkc1p resulted in very-slow-growing cells.

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Section: Resultsmentioning

confidence: 99%

Transcript Profiles of Candida albicans Cortical Actin Patch Mutants Reflect Their Cellular Defects: Contribution of the Hog1p and Mkc1p Signaling Pathways

et al. 2006

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“…1C), although it is unknown whether the Cla4 PH domain binds phosphoinositides. Finally, phosphoinositide kinase mutants are available to determine whether Cla4 is regulated by phosphoinositide production (17)(18)(19)(20)(21).…”

Section: Resultsmentioning

confidence: 99%

“…Stt4 and Mss4 synthesize, respectively, PI4P and PI4,5P2 on the plasma membrane and are required for polarization of the actin cytoskeleton (17)(18)(19)(20). Pik1 synthesizes the Golgi pool of PI4P and promotes secretion but apparently is uninvolved in cell or actin polarization (19,21).…”

Section: Resultsmentioning

confidence: 99%

“…Phosphoinositide signaling has several functions in yeast. The type III PI 4-kinase Stt4 and the PI4P 5-kinase Mss4 are required for polarization of the cortical actin cytoskeleton and regulation of a protein kinase C-activated MAP kinase cascade (17)(18)(19)(20). The Golgi-localized type III PI 4-kinase Pik1 regulates trafficking through the Golgi apparatus (19,21).…”

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confidence: 99%

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The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate

Wild

Lemmon

et al. 2004

Journal of Biological Chemistry

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Signal transduction pathways that co-regulate a given biological process often are organized into networks by molecules that act as coincidence detectors. Phosphoinositides and the Rho-type GTPase Cdc42 regulate overlapping processes in all eukaryotic cells. However, the coincidence detectors that link these pathways into networks remain unknown. Here we show that the p21-activated protein kinase-related kinase Cla4 of yeast integrates signaling by Cdc42 and phosphatidylinositol 4-phosphate (PI4P). We found that the Cla4 pleckstrin homology (PH) domain binds in vitro to several phosphoinositide species. To determine which phosphoinositides regulate Cla4 in vivo, we analyzed phosphatidylinositol kinase mutants (stt4, mss4, and pik1). This indicated that the plasma membrane pool of PI4P, but not phosphatidylinositol 4,5-bisphosphate or the Golgi pool of PI4P, is required for localization of Cla4 to sites of polarized growth. A combination of the Cdc42-binding and PH domains of Cla4 was necessary and sufficient for localization to sites of polarized growth. Point mutations affecting either domain impaired the ability of Cla4 to regulate cell morphogenesis and the mitotic exit network (localization of Lte1). Therefore, Cla4 must retain the ability to bind both Cdc42 and phosphoinositides, the hallmark of a coincidence detector. PI4P may recruit Cla4 to the plasma membrane where Cdc42 activates its kinase activity and refines its localization to cortical sites of polarized growth. In mammalian cells, the myotonic dystrophy-related Cdc42-binding kinase possesses p21-binding and PH domains, suggesting that this kinase may be a coincidence detector of signaling by Cdc42 and phosphoinositides.

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“…Phosphoinositols are critical small signaling molecules that regulate cellular functions. The synthesis of PI4,5P 2 is essential for sporulation, endocytosis, membrane trafficking, and normal organization of the actin cytoskeleton (14,15). In a bcp1 mutant, Mss4 accumulated in the nucleus, resulting in reduced levels of PI4,5P 2 in the cell (11).…”

mentioning

confidence: 99%

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

Ting

Johnson

et al. 2017

Journal of Biological Chemistry

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Edited by Linda SpremulliEukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins. Bcp1 has been shown to be necessary for the export of Mss4, a phosphatidylinositol 4-phosphate 5-kinase, and required for ribosome biogenesis. However, its specific function in ribosome biogenesis has not been described. Here, we show that Bcp1 dissociates Rpl23 from the karyopherins and associates with Rpl23 afterward. Loss of Bcp1 causes instability of Rpl23 and deficiency of 60S subunits. In summary, Bcp1 is a novel 60S biogenesis factor via chaperoning Rpl23 in the nucleus.The ribosome is a large macromolecular complex responsible for decoding cellular genetic information into proteins. There are two ribosomal subunits; in the eukaryotes, they are the (60S) large subunit and the small (40S) subunit, each composed of both rRNAs and ribosomal proteins. In eukaryotic cells, the assembly of ribosomes occurs in the nucleolus, a subcompartment of the nucleus devoted to ribosome biogenesis. rRNAs are transcribed by RNA polymerase I and III, and the initial assembly and processing events occur co-transcriptionally. The mRNAs of ribosomal proteins are transcribed in the nucleus by RNA polymerase II and translated in the cytoplasm. Consequently, the ribosomal proteins must be imported into the nucleus for assembly with the rRNAs. After ribosome assemblies have achieved a certain stage of maturation, export factors are loaded to direct these huge complexes to cross the nuclear membrane through the nuclear pore complexes (1-6). In the cytoplasm, ribosomes undergo additional steps in the maturation process; the trans-acting factors that are exported with nascent ribosomal subunits need to be stripped off, additional ribosomal proteins are added, and in the case of the 40S subunit, the final rRNA processing occurs (7,8). The synthesis of ribosomes requires the coordination of many non-ribosomal trans-acting factors at different stages for this pathway to be completed. About 200 trans-acting factors are involved in rRNA processing, rRNA folding, protein loading, and export. To date, more trans-acting factors have continued to be identified (7, 9, 10).BCP1 is an essential gene involved in the export of Mss4 (11), a phosphatidylinositol (PI) 2 4-phosphate 5-kinase that catalyzes the phosphorylation of PI4-phosphate and acts with the PI4-kinase, Stt4p, at the plasma membrane to generate PI4,5P 2 (12, 13). Phosphoinositols are critical small signal...

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Stt4 PI 4-Kinase Localizes to the Plasma Membrane and Functions in the Pkc1-Mediated MAP Kinase Cascade

Cited by 243 publications

References 56 publications

Transcript Profiles of Candida albicans Cortical Actin Patch Mutants Reflect Their Cellular Defects: Contribution of the Hog1p and Mkc1p Signaling Pathways

Transcript Profiles of Candida albicans Cortical Actin Patch Mutants Reflect Their Cellular Defects: Contribution of the Hog1p and Mkc1p Signaling Pathways

The p21-activated Protein Kinase-related Kinase Cla4 Is a Coincidence Detector of Signaling by Cdc42 and Phosphatidylinositol 4-Phosphate

Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

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