Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 426

Cell migration actually requires degradation and reformation of focal adhesions.
Major components of focal adhesions include focal adhesion kinase, paxillin, 65
tensin, vinculin, BCAR1 docker, and SRC family kinases. Cell migration is actually
associated with phosphorylation of focal adhesion components as well as proteolysis
by metallopeptidases and calpain. Integrin ligation and aggregation stimulates local
accumulation and binding of structural proteins, such as -actinin and vinculin.

Integrin clustering recruits not only structural proteins, but also signaling compo-
nents, such as small GTPases, p21-activated kinases, extracellular signal-regulated
kinase, and focal adhesion kinase. Integrin-mediated cell adhesion indeed initiates
signaling cascades characterized by phosphorylation of focal adhesion proteins,
such as focal adhesion kinase and inter-protein interaction mediator BCAR1 that
is phosphorylated by Src family kinases recruited by autophosphorylated focal
adhesion kinase [ 785 ]. 66
Monomeric GTPases (CDC42, Rac, Ras, and Rho) regulate actin-binding pro-
teins (ARP2-ARP3, Dia, VASP, and WASP) to promote actin nucleation and
filament extension at barbed ends, particularly at the cell cortex. 67 Small RhoA
GTPase activates RoCK1 and RoCK2 in vascular smooth myocytes. In addition,
activated RhoA stimulates its effector RoCK that can phosphorylate myosin-2, in
addition to its Ca 2 + -dependent activation by myosin light chain kinase. Kinase
RoCK also phosphorylates (inactivates) the myosin-binding subunit of myosin light
chain phosphatase. Moreover, RoCK promotes actin polymerization, as it activates
LIM kinase. Activated Rac1 and Rac2 also favor SMC migration, as they both
stimulate PAK kinase.

α

8.5.8 Vasomotor Tone

The vascular response, especially in arterioles, to changes in intravascular pressure
( p i ) is vasoconstriction or vasodilation, whether p i heightens or decays [ 786 ]. Blood
flow regulates vessel caliber: (1) quickly by vasomotor tone changes; (2) later by
stimulated gene expression and structural reorganization when loading is main-
tained, and (3) chronically by wall remodeling (adaptative changes). Studies have
been aimed at identifying the sequence of cellular events, from sensing to reaction,
responsible for vasomotor activity and SMC responsiveness, independently of

65 Paxillin joins nascent focal adhesion complex formed by G-protein-receptor kinase-interacting
protein GIT1, p21-activated kinase, and RhoGEF6 and/or RhoGEF7.
66 Docking protein BCAR1 (CAS or P130CAS), together with CRK adaptor, also connects guanine
nucleotide-exchange factors RapGEF1 and SOS once integrin is activated.
67 Members of the Wiskott-Aldrich syndrome protein family are involved in signal transduction
from receptors to the actin cytoskeleton. They interact with small GTPase CDC42 and cy-
toskeletal organizing ARP2-ARP3 complexes. Diaphanous is a Rho effector involved in actin
polymerization. Vasodilator-stimulated phosphoprotein binds both

G actin and F actin. It regulates

integrin-matrix interactions. It is regulated by PKA and PKG kinases.