Biology Reference
In-Depth Information
Figure 11.6 Postulated signalling pathways for the early and late actin polymerization
transients in response to EGF. Pathways 1 and 2 are described in the text and are
proposed to be distinct pathways involving; (1) PLC-stimulated cofilin generation of
barbed ends and actin polymerization in a PI3K-independent step. This would be
stimulated further by an increase in pH through the action of PKC on Na/H exchangers.
(2) A positive feedback loop between PI3K and Rac causing repeated stimulation of
WASp family members (WASp
f
) and the Arp2/3 complex leading to actin polymerization.
Actin filaments polymerized proximal to the receptor by pathway 61 could participate in
the assembly of the F-actin-dependent EGF receptor signalling complex (Heyden et al.,
1997; Payrastre et al., 1991) and supply filaments to support the F-actin-dependent
positive feedback loop for PIP
3
production involving PI3K and Rac (Orion et al., 2002).
This positive feedback loop is postulated here to be required for the activation of the late
actin polymerization response
Payrastre et al., 1991). This complex is postulated to recruit PI3K and
establish the F-actin-dependent positive feedback loop of pathway 2
believed to be required for the maintenance of asymmetry needed for
chemotaxis (Orion et al., 2002). In addition, the activation of the Na/H
exchanger by the activated protein kinase C (PKC) in this complex would
cause activation of cofilin by an increase in pH proximal to the receptor
increasing cofilin's severing activity (Bernstein et al., 2000). Further work
will be needed to determine if pathways 1 and 2 exist as distinct entities
