Mitogen activated protein kinases (MAPKs) comprise an evolutionarily conserved family of signal transducing enzymes that phosphorylate regulatory molecules in response to a broad variety of upstream signals. MAPKs are required for adaptive responses to changes in the environment, proliferative responses to mitogens, and differentiative responses to signals that occur during development. An important issue that is relevant to embryological development and the control of cell proliferation concerns how MAPK pathways regulate developmental processes. SMK1, encodes a MAPK that is required for meiotic development an excellent model system for development. This study will use SMK1 and sporulation to elucidate molecular mechanisms in MAPK signaling pathways that regulate cellular differentiation programs. A collection of conditional smk1 mutants has already been generated and characterized at the genetic, biochemical and ultrastructural levels (Wagner et al. 1999, Genetics 151:1327).
In aim 1 of this proposal these mutants will be used to: Identify new components of the SMK1 signaling pathways using sensitized genetic backgrounds. In order to ground the inferences from these genetic studies in biochemical mechanism it is necessary to develop biochemical approaches to study Smk1.
In aim 2 studies we will: Elucidate the role of the spindle pole body in regulating SMK1 function. In cells (Pierce et a. 1998, Mol. Cell. Biol. 18:5970, i.e. et al. EMO J. in press).
In aim 4 experiments are described that will: Elucidate the role of the SMK1 transcriptional regulatory pathway in controlling progression of meiotic development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061817-04
Application #
6619645
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Anderson, Richard A
Project Start
2000-08-01
Project End
2004-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
4
Fiscal Year
2003
Total Cost
$222,600
Indirect Cost
Name
Thomas Jefferson University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Shin, Marcus E; Skokotas, Aikaterini; Winter, Edward (2010) The Cdk1 and Ime2 protein kinases trigger exit from meiotic prophase in Saccharomyces cerevisiae by inhibiting the Sum1 transcriptional repressor. Mol Cell Biol 30:2996-3003
McDonald, Christine M; Wagner, Marisa; Dunham, Maitreya J et al. (2009) The Ras/cAMP pathway and the CDK-like kinase Ime2 regulate the MAPK Smk1 and spore morphogenesis in Saccharomyces cerevisiae. Genetics 181:511-23
Ahmed, Noreen T; Bungard, David; Shin, Marcus E et al. (2009) The Ime2 protein kinase enhances the disassociation of the Sum1 repressor from middle meiotic promoters. Mol Cell Biol 29:4352-62
Moore, Michael; Shin, Marcus E; Bruning, Adrian et al. (2007) Arg-Pro-X-Ser/Thr is a consensus phosphoacceptor sequence for the meiosis-specific Ime2 protein kinase in Saccharomyces cerevisiae. Biochemistry 46:271-8
Schindler, Karen; Winter, Edward (2006) Phosphorylation of Ime2 regulates meiotic progression in Saccharomyces cerevisiae. J Biol Chem 281:18307-16
McDonald, Christine M; Cooper, Katrina F; Winter, Edward (2005) The Ama1-directed anaphase-promoting complex regulates the Smk1 mitogen-activated protein kinase during meiosis in yeast. Genetics 171:901-11
Bungard, David; Reed, Michelle; Winter, Edward (2004) RSC1 and RSC2 are required for expression of mid-late sporulation-specific genes in Saccharomyces cerevisiae. Eukaryot Cell 3:910-8
Schaber, Michael; Lindgren, Anne; Schindler, Karen et al. (2002) CAK1 promotes meiosis and spore formation in Saccharomyces cerevisiae in a CDC28-independent fashion. Mol Cell Biol 22:57-68