Abstract

The long-term goal of the proposed studies is to understand the biochemical properties and cellular regulation of protein kinases that control myosin localization in Dictyostelium. The goal of the proposed studies is to describe the fundamental biochemical properties and structure of MHCK-A and the related MHCK B.
Four specific aims are proposed: (1) To determine which residues and regions of MHCK A are involved in catalytic function and substrate binding; (2) to determine the biochemical and physiological substrate specificity of MHCK B; (3) to determine if there are conserved autoinhibitory or activating motifs in different members of the MHCK family of kinases; and (4) to determine the roles of the WD-repeat domain in MHCK A.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050009-07
Application #
2857185
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1993-08-01
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Physiology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Rai, Vandana; Thomas, Dustin G; Beach, Jordan R et al. (2017) Myosin IIA Heavy Chain Phosphorylation Mediates Adhesion Maturation and Protrusion in Three Dimensions. J Biol Chem 292:3099-3111
Thomas, Dustin; Thiagarajan, Praveena S; Rai, Vandana et al. (2016) Increased cancer stem cell invasion is mediated by myosin IIB and nuclear translocation. Oncotarget 7:47586-47592
Gupta, Sounak; Hau, Andrew M; Al-Ahmadie, Hikmat A et al. (2016) Transforming Growth Factor-? Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion. Am J Pathol 186:1351-60
Southern, Brian D; Grove, Lisa M; Rahaman, Shaik O et al. (2016) Matrix-driven Myosin II Mediates the Pro-fibrotic Fibroblast Phenotype. J Biol Chem 291:6083-95
Pasapera, Ana M; Plotnikov, Sergey V; Fischer, Robert S et al. (2015) Rac1-dependent phosphorylation and focal adhesion recruitment of myosin IIA regulates migration and mechanosensing. Curr Biol 25:175-186
Thomas, Dustin G; Yenepalli, Aishwarya; Denais, Celine Marie et al. (2015) Non-muscle myosin IIB is critical for nuclear translocation during 3D invasion. J Cell Biol 210:583-94
Thiagarajan, Praveena S; Hitomi, Masahiro; Hale, James S et al. (2015) Development of a Fluorescent Reporter System to Delineate Cancer Stem Cells in Triple-Negative Breast Cancer. Stem Cells 33:2114-2125
Crish, James; Conti, Mary Anne; Sakai, Takao et al. (2013) Keratin 5-Cre-driven excision of nonmuscle myosin IIA in early embryo trophectoderm leads to placenta defects and embryonic lethality. Dev Biol 382:136-48
Chandrasekharan, Unni M; Dechert, Lisa; Davidson, Uchechukwu I et al. (2013) Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor receptor 2 is required for target gene expression. Sci Signal 6:ra60
Gupta, Sounak; Hau, Andrew M; Beach, Jordan R et al. (2013) Mammalian target of rapamycin complex 2 (mTORC2) is a critical determinant of bladder cancer invasion. PLoS One 8:e81081

Showing the most recent 10 out of 20 publications