Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • June 22, 2015

Research

keywords

  • Adenylyl Cyclases
  • Antigens, CD
  • Cyclic AMP-Dependent Protein Kinases
  • Endothelial Cells
  • Leukocytes
  • Signal Transduction
  • Transendothelial and Transepithelial Migration

Identity

PubMed Central ID

  • PMC4493416

Scopus Document Identifier

  • 84942844075

Digital Object Identifier (DOI)

  • 10.1074/jbc.M608657200

PubMed ID

  • 26101266

Additional Document Info

volume

  • 212

issue

  • 7