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D Kellogg

Publications and source records attributed to D Kellogg.

10 recordsLinked to original sources
PubMed1999

Septins: cytoskeletal polymers or signalling GTPases?

Septins are a family of conserved proteins that have been implicated in a variety of cellular functions involving specialized regions of the cell cortex and changes in cell shape. The biochemistry and localization of septins suggest that they form a novel cytoskeletal system or that they function as scaffolds for the assembly of signalling complexes. This article discusses septin biochemistry and septin-interacting proteins, focusing on the missing link between the structure and biochemical properties of septin proteins, and on how they function at a molecular level in processes such as cytokinesis and yeast budding.

Animals↗
PubMed1999

The elm1 kinase functions in a mitotic signaling network in budding yeast.

In budding yeast, the Clb2 mitotic cyclin initiates a signaling network that negatively regulates polar bud growth during mitosis. This signaling network appears to require the function of a Clb2-binding protein called Nap1, the Cdc42 GTPase, and two protein kinases called Gin4 and Cla4. In this study, we demonstrate that the Elm1 kinase also plays a role in the control of bud growth during mitosis. Cells carrying a deletion of the ELM1 gene undergo a prolonged mitotic delay, fail to negatively regulate polar bud growth during mitosis, and show defects in septin organization. In addition, Elm1 is required in vivo for the proper regulation of both the Cla4 and Gin4 kinases and interacts genetically with Cla4, Gin4, and the mitotic cyclins. Previous studies have suggested that Elm1 may function to negatively regulate the Swe1 kinase. To further understand the functional relationship between Elm1 and Swe1, we have characterized the phenotype of Deltaelm1 Deltaswe1 cells. We found that Deltaelm1 Deltaswe1 cells are inviable at 37 degrees C and that a large proportion of Deltaelm1 Deltaswe1 cells grown at 30 degrees C contain multiple nuclei, suggesting severe defects in cytokinesis. In addition, we found that Elm1 is required for the normal hyperphosphorylation of Swe1 during mitosis. We propose a model in which the Elm1 kinase functions in a mitotic signaling network that controls events required for normal bud growth and cytokinesis, while the Swe1 kinase functions in a checkpoint pathway that delays nuclear division in response to defects in these events.

Animals↗
PubMed1998

The septins are required for the mitosis-specific activation of the Gin4 kinase.

In budding yeast, a protein kinase called Gin4 is specifically activated during mitosis and functions in a pathway initiated by the Clb2 cyclin to control bud growth. We have used genetics and biochemistry to identify additional proteins that function with Gin4 in this pathway, and both of these approaches have identified members of the septin family. Loss of septin function produces a phenotype that is very similar to the phenotype caused by loss of Gin4 function, and the septins are required early in mitosis to activate Gin4 kinase activity. Furthermore, septin mutants display a prolonged mitotic delay at the short spindle stage, consistent with a role for the septins in the control of mitotic events. Members of the septin family bind directly to Gin4, demonstrating that the functions of Gin4 and the septins must be closely linked within the cell. These results demonstrate that the septins in budding yeast play an integral role in the mitosis-specific regulation of the Gin4 kinase and that they carry out functions early in mitosis.

Amino Acid Sequence↗
PubMed1998

Control of mitotic events by the Cdc42 GTPase, the Clb2 cyclin and a member of the PAK kinase family.

BACKGROUND: Cyclins and cyclin-dependent kinases induce and coordinate the events of the cell cycle, although the mechanisms by which they do so remain largely unknown. In budding yeast, a pathway used by the Clb2 cyclin to control bud growth during mitosis provides a good model system in which to understand how cyclin-dependent kinases control cell-cycle events. In this pathway, Clb2 initiates a series of events that lead to the mitosis-specific activation of the Gin4 protein kinase. A protein called Nap1 is required in vivo for the activation of Gin4, and is able to bind to both Gin4 and Clb2. We have used a simple genetic screen to identify additional proteins that function in this pathway. RESULTS: We have found that the Cdc42 GTPase and a member of the PAK kinase family called Cla4 both function in the pathway used by Clb2 to control bud growth during mitosis. Cdc42 and Cla4 interact genetically with Gin4 and Nap1, and both are required in vivo for the mitosis-specific activation of the Gin4 kinase. Furthermore, Cla4 undergoes a dramatic hyperphosphorylation in response to the combined activity of Nap1, the Clb2-Cdc28 kinase complex, and the GTP-bound form of Cdc42. Evidence is presented which suggests that the hyperphosphorylated form of Cla4 is responsible for relaying the signal to activate Gin4. CONCLUSIONS: Previous studies have suggested that cyclin-dependent kinases control the cell cycle by directly phosphorylating proteins involved in specific events, such as nuclear lamins, microtubule-associated proteins and histones. In contrast, our results demonstrate that the Clb2-Cdc28 cyclin-dependent kinase complex controls specific cell-cycle events through a pathway that involves a GTPase and at least two different kinases. This suggests that cyclin-dependent kinases may control many cell-cycle events through GTPase-linked signaling pathways that resemble the intricate signaling pathways known to control many other cellular events.

Cell Cycle↗
PubMed1997

Control of mitotic events by Nap1 and the Gin4 kinase.

Little is known about the pathways used by cyclins and cyclin-dependent kinases to induce the events of the cell cycle. In budding yeast, a protein called Nap1 binds to the mitotic cyclin Clb2, and Nap1 is required for the ability of Clb2 to induce specific mitotic events, but the role played by Nap1 is unclear. We have used genetic and biochemical approaches to identify additional proteins that function with Nap1 in the control of mitotic events. These approaches have both identified a protein kinase called Gin4 that is required for the ability of Clb2 and Nap1 to promote the switch from polar to isotropic bud growth that normally occurs during mitosis. Gin4 is also required for the ability of Clb2 and Nap1 to promote normal progression through mitosis. The Gin4 protein becomes phosphorylated as cells enter mitosis, resulting in the activation of Gin4 kinase activity, and the phosphorylation of Gin4 is dependent upon Nap1 and Clb2 in vivo. Affinity chromatography experiments demonstrate that Gin4 binds tightly to Nap1, indicating that the functions of these two proteins are closely tied within the cell. These results demonstrate that the activation of Gin4 is under the control of Clb2 and Nap1, and they provide an important step towards elucidating the molecular pathways that link cyclin-dependent kinases to the events they control.

Base Sequence↗
PubMed1988

Regulation of microtubule protein levels during cellular morphogenesis in nerve growth factor-treated PC12 cells.

Nerve growth factor induces neurite process formation in pheochromacytoma (PC12) cells and causes the parallel increase in levels of the microtubule-associated proteins, tau and MAP1, as well as increases in tubulin levels. Mechanisms to insure balanced accumulation of microtubule proteins and make their levels highly responsive to nerve growth factor were investigated. The effects on tau, MAP1, and tubulin are due to changes in protein synthesis rates, which for tau and tubulin we could show are due in part to changes in the mRNA levels. Whereas tubulin shows feedback regulation to modulate synthesis up or down, tau protein synthesis is not affected in a straightforward way by microtubule polymerization and depolymerization. The degradation of tau, MAP1, and both tubulin polypeptides, however, are stimulated by microtubule depolymerization caused by colchicine, or nerve growth factor removal. Combined feedback on synthesis and stability make tubulin levels highly responsive to assembly states. In addition, the linkage of tau and MAP1 turnover with the state of microtubule polymerization amplifies any change in their rate of synthesis, since tau and MAP1 promote microtubule polymerization. This linkage lends itself to rapid changes in the state of the system in response to nerve growth factor.

Animals↗
PubMed1988

Characterization of a sequence of human T cell leukemia virus type I from a patient with chronic progressive myelopathy.

DNA from peripheral blood mononuclear cells of individuals with chronic progressive myelopathy (CPM) were extensively analyzed for the presence of human T cell leukemia virus (HTLV) type I-like sequences by using the polymerase chain reaction. The DNA samples were amplified with oligonucleotides from three separate regions of HTLV viral genomes. A portion of the amplified viral genome from a representative patient was sequenced after molecular cloning into bacteriophage M13. Sequence data indicate that HTLV type I and not a related virus is associated with CPM.

Aged↗