Specificity between two yeast MAPK pathways

120802 CSHL CCB programProject Proposal Presentation

Kengo WatanabeCell Signaling, Grad. Sch. Pharmaceut. Sci.,

Univ. of Tokyo, Japan

Many complicated signals go around in cell.

http://en.wikipedia.org/wiki/MAPK/ERK_pathway

Sword fighters in Japanese cartoon

Many complicated signals go around in cell.

http://en.wikipedia.org/wiki/MAPK/ERK_pathway

Stress-responsive Mitogen-Activated Protein Kinase (MAPK) pathway

Stress

Cell

ROS, UV, Osmotic stress,Heat, Bacterial Infection, etc.

Response Apoptosis, Inflammation,Cell swelling/shrinkage, etc.

MAP3K

MAP2K

MAPK

MAPKpathway

Each phosphorylation reaction = Michaelis-Menten equation

MAP3K MAP3KP

MAPK MAPKP

MAP2K MAP2KP

Stress

Response

Activated!!

Activated!!

Activated!!

Michaelis-menten equation

Pheromone pathway & High-osmolarity pathway

Why cross-talk is NOT occurred?

http://es.wikipedia.org/wiki/Saccharomyces_cerevisiae

Yeast!!

McClean M.N., et al. Nat Genet., 39, 2007

MAP3K

MAP2K

MAPK

The models of McClean et al.

“Cross-talk and decision making in MAP kinase pathways.”McClean M.N., et al. Nat. Genet., 39, 2007

Simultaneous stimuli enables us to distinguish between two pathways

Cross-talk

Switch-like

Only Y3 activation

Only X3 activation

Bistable

McClean group concluded “mutual inhibition” achieved the specificity.

GFP = Signal1 pathway activation

RFP = Signal2 pathw

ay activation

Patterson et al. insisted “insulation”, not “mutual inhibition” achieved.

“Single-cell analysis reveals that insulation maintains signaling specificity between two yeast MAPK pathways with common components.”Patterson J.C., et al. Sci. Signal., 19, 2010

Future Plan

Reproduction of McClean’s model

Change their model

Explain Patterson’s result