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Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate
leukocyte transendothelial migration
#MMPMID26101266
Watson RL
; Buck J
; Levin LR
; Winger RC
; Wang J
; Arase H
; Muller WA
J Exp Med
2015[Jun]; 212
(7
): 1021-41
PMID26101266
show ga
CD99 is a critical regulator of leukocyte transendothelial migration (TEM). How
CD99 signals during this process remains unknown. We show that during TEM,
endothelial cell (EC) CD99 activates protein kinase A (PKA) via a signaling
complex formed with the lysine-rich juxtamembrane cytoplasmic tail of CD99, the
A-kinase anchoring protein ezrin, and soluble adenylyl cyclase (sAC). PKA then
stimulates membrane trafficking from the lateral border recycling compartment to
sites of TEM, facilitating the passage of leukocytes across the endothelium.
Pharmacologic or genetic inhibition of EC sAC or PKA, like CD99 blockade, arrests
neutrophils and monocytes partway through EC junctions, in vitro and in vivo,
without affecting leukocyte adhesion or the expression of relevant cellular
adhesion molecules. This is the first description of the CD99 signaling pathway
in TEM as well as the first demonstration of a role for sAC in leukocyte TEM.
|12E7 Antigen
[MESH]
|Adenylyl Cyclases/*metabolism
[MESH]
|Analysis of Variance
[MESH]
|Animals
[MESH]
|Antibodies, Monoclonal/immunology
[MESH]
|Antigens, CD/immunology/*metabolism
[MESH]
|Blotting, Western
[MESH]
|Cyclic AMP-Dependent Protein Kinases/*metabolism
[MESH]
free
free
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