Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 536

endothelial cells. This second messenger triggers cell contraction as well as
transport of intracellular vesicles, especially those that carry adhesion molecules
used for endothelial transmigration.
In addition, clusters of adhesion molecules activate Src and mitogen-activated
protein kinases as well as monomeric Rac1, RhoA, and RhoG GTPases. Both Rac1
and RhoA promote contraction of actomyosin-based stress fibers. Both Rac1 and
RhoG intervene in the formation of apical protrusions that generate to docking
structures [ 980 ].
Small Rac1 GTPase favors the activation of endothelial NADPH oxidase NOx2
that generates reactive oxygen species. These substances, in turn, regulate the
activity of protein kinases, such as protein kinase-C, focal adhesion kinase FAK2,
as well as PTPn1 phosphatase, to control the phosphorylation state of junctional
proteins [ 980 ].
Small GTPases participate in feedback loops. Binding of ICAM1 to leukocyte
integrins launches recruitment of actin- and ICAM1-binding proteins cortactin
and filamin that enhance ICAM1 clustering [ 980 ]. In addition, RhoA GTPase
is activated on ICAM1 clustering and, in turn, promotes clustering of ICAM1,
VCAM1, and E-selectin [ 980 ].
In endothelial cells, clusters of ICAM1 molecules linked to the cortical actin net-
work via actin-binding adaptors (

-actinin, cortactin, ezrin, radixin, and moesin, as
well as filamin, paxillin, and vinculin) reorganize the cytoskeleton and intercellular
junctions. 100
Filamentous actin-binding lymphocyte-specific protein LSP1 101 expressed by
leukocytes and endothelial cells is a substrate of MAPK-activated protein kinase
MAPKAPK2 subtype. Phosphorylation of LSP1 is impeded by P38MAPK, an
upstream kinase for MAPKAPK2 [ 982 ]. 102

α

9.7.5 Intracellular Signaling in Leukocytes

Integrins are activated by chemokine receptors during adhesion of platelets and
leukocytes onto activated endothelial cells. During the first stage of extravasation,
blood cells interact owing to integrins.

100

-Actinin is a Ca 2 + -regulated antiparallel crosslinker of actin filaments that participates in the
maturation of small, nascent adhesions [ 980 ]. Filamin crosslinks actin filaments in orthogonal actin
networks.

α

-Actinin and filamin cooperate to elevate actin mesh stiffness. They may also enhance
the stability of docking structures.
101 A.k.a. 47-kDa actin-binding protein and 52-kDa phosphoprotein (PP52).
102 In neutrophils, LSP1 P

α

F actin polarization during

localizes to lamellipodium and stabilizes

neutrophil chemotaxis.