|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1998 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1997 : ¥2,300,000 (Direct Cost : ¥2,300,000)
Dictyostelium cells chemotax toward folic acid in the vegetative stage and cAMP in the aggregation stage. These chemoattractants have been shown to elicit adenylyl cyclase activation. Recently, it was revealed that MAP-kinase ERK2 is involved in the activation of adenylyl cyclase by extracellular cAMP in Dictyostelium cells (Maeda et al., 1996). We also found that ERK2 is negatively regulated by ras and also regulated by cAMP-dependent protein kinase in a postive feed-back (Aubry et al., 1997). Here, I investigated whether the activation of adenylyl cyclase by folic acid is also mediated by ERK2. In this consequence, I found that ERK2 is transiently activated by folic acid, this activation is mediated through a heterotrimeric G-protein, and the alpha-subunit coupling to this G-protein is G-alpha4 (Maeda& Firtel, 1997). Further, I revealed that monapterin, a derivative of folic acid, also activates ERK2. As monapterin attracts Dictyostelium cells only in the later developmental stages than the aggregation stage, ERK2 activation by monapterin may suggest that cell-cell communication in the late developmental stage is mediated through monapterin-like protein secreted by cells themselves.
I also examined the effects of DIE-1 and ammonia, other importants extracellular compounds involved in cell differentiation. Both compounds did not exert any significant effect on ERK2 (unpublished).