October 29, 2008
Integrin-regulated FAK-Src and integrin linked kinase signaling: focal
adhesion, cell motility, and chondrogenesis.
Text was taken verbatim from the cited textbook and research publications.
Alberts, Molecular Biology of the Cell, 4th Ed
and Lodish Molecular
Cell Biology 4th Edition
Activation of the FAK-Src complex and cell motility
Before examining how integrins promote cell migration via the activation of the
FAK-Src complex, it is necessary to re-examine some topics covered in BIO250: the
molecular basis of actin-myosin contractions in non-muscle cells, the activation of small
monomeric GTPases, and the hierarchy of focal contacts between integrins and ECM
Actinomyosin contractions in non-muscle cells
While actin polymerization can push plasma membranes to generate cellular
protrusions at the leading edge, movement of cells is also dependent on the interaction of
actin cytoskeleton with myosin motors.
Myosin motors move along actin filament by
hydrolysis of ATP to transform chemical energy into mechanical energy- hence myosin
motors are often referred to as
. Alberts, 4th edition, gives a
description of the several members of the myosin family. The focused of the course is on
myosin I and myosin II as they play key roles in promoting cellular movements.
figure 18-20 for a schematic of myosin motors.
The tail domain determines specific
functions of the motors.
The tail of myosin I interacts with lipid bilayers, by a still poorly
Via its interactions with the plasma membrane and actin-
filaments at the leading edge of migrating cells, it’s hypothesized that myosin I promotes
lamellipodia and filopodia extensions.
Myosin II, in a manner similar to its role in
sarcomere contractions in muscle cells, promotes contraction of stress fibers and the
formation of focal adhesion.
A property exhibited by all moving cells is polarity; that is, certain structures
always form at the front of the cell, whereas others are found at the rear.
is initiated by the formation of a large, broad membrane protrusion at the leading edge of
Video microscopy reveals that a major feature of this movement is the
polymerization of actin at the membrane.
In addition, actin filaments at the leading edge
are rapidly cross-linked into bundles and networks in a protruding region, called a
lamellipodia in vertebrate cells.
In some cases, slender, fingerlike membrane
projections, called filopodia, are also extended from the leading edge.
then form stable contacts with the underlying surface and prevent the membrane form
(In some cases, filopodia act like antennae, promoting retraction).
Actin dynamics and force generation by myosin II motors