Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 456

Catenin- δ 1 regulates cadherin-5 expression and insertion into the plasma

membrane. The Ctnn 1-Cdh5 complex precludes binding of ubiquitin ligase

Hakai, hence preventing cadherin-5 degradation. Catenin-

δ

1 also has many partners,
such as microtubule nanomotor kinesin and regulatory kinases and phosphatases
(e.g., SRC kinase family member Fyn, FRK family kinase Fer, and plasmalemmal
PTPRm and cytosolic PTPn6 protein Tyr phosphatases) [ 854 ]. Unlike

δ

β -catenin

and plakoglobin, catenin- 1 does not associate with the actin cytoskeleton, but

with microtubules. However, catenin-

δ

1 regulates the contractile apparatus of
endothelial cells and modulates endothelium permeability. The Ctnn

δ

1-Cdh5
complex actually impedes the activity of RhoA GTPase that mediates myosin
light chain phosphorylation and actin stress fiber formation.
Several receptor and cytoplasmic protein Tyr phosphatases localize to adherens
junctions and can dephosphorylate components of the cadherin-catenin complex
and control Rho activity.
Vascular endothelial protein Tyr phosphatase PTPRb restricted to the
endothelium associates specifically with and dephosphorylates VE-cadherin.
Moreover, the PTPRb-Cdh5 complex can contribute to strengthening of adherens
junction barrier by a phosphatase-independent mechanism [ 854 ].
Phosphatase PTPRj 12 abounds in endothelial cells at least in arteries and
capillaries of several organs [ 853 ]. When it associates with the Cdh5-

δ

Ctn complex,
it dephosphorylates VEGFR2 vascular endothelial growth factor receptor.
Receptor-like protein Tyr phosphatase PTPRm is strongly present in endothelial
junctions of arteries and continuous capillaries. Phosphatase PTPRm dephospho-
rylates catenin-

β

δ 1, thus modulating interaction of catenin- δ 1 with cadherin-5 and

controlling catenin- 1 regulation of RhoA activity.

Protein Tyr phosphatase PTPn11 is an additional component of adherens
junctions that links to VE-cadherin. Dissociation of PTPn11 can expose junctional
proteins to phosphorylation by kinases and cause adherens junction disassembly.
In addition, PTPn11 prevents small GTPase RhoA activity to stabilize adherens
junction.
Small GTPases CDC42, Rac, and RhoA contribute to the regulation of ad-
herens junctions. Bradykinin, histamine, platelet-activating factor, and thrombin
that heighten endothelial permeability provoke disassembly of adherens junctions
via RhoA GTPase. On the other hand, Rac GTPase promotes endothelial barrier
by stabilizing adherens junctions. Moreover, activated CDC42 is involved in refor-
mation of adherens junctions in endothelial cells during recovery from abnormal
permeability induced by permeability-increasing agents. Small GTPases CDC42
and Rac modulate interactions between

δ

-catenin and the cadherin-catenin complex
to favor formation of adherens junctions. Activated CDC42 and Rac indeed interact
with

α

β -catenin-sequestering protein IQGAP to free β -catenin that can then binds

with its partners cadherin and α -catenin [ 854 ].

12 A.k.a. PTP

η η

,RPTP , CD148, and Density-enhanced phosphatase DEP1.