Mechanisms that generate cell polarity in wounded monolayers
of fibroblasts. LPA-treatment of wounded monolayers leads
to activation of Cdc42. Cdc42 activates two pathways that
lead to cell polarity. In the nuclear movement pathway
(left arm of diagram at left), Cdc42 activates myotonic
dystrophy kinase-related Cdc42-binding kinase (MRCK),
which phosphorylates and activates myosin II, leading to
actin cable flow and TAN line formation to move the
nucleus. Cdc42 simultaneously activates a second
centrosome centration pathway (right arm in the diagram at
left), which involves Par6/PKCζ, Par3, dynein/dynactin,
and microtubules and holds the centrosome in the centroid
of the cell. The schematic diagram at the right shows
microtubules, actin cables, TAN lines, and dynein during
cell polarization. (A color version of this figure is
available in the online journal.)