A Poxvirus-Encoded Semaphorin Induces Cytokine Production from Monocytes and Binds to a Novel Cellular Semaphorin Receptor, VESPR

Abstract

The vaccinia virus A39R protein is a member of the semaphorin family. A39R.Fc protein was used to affinity purify an A39R receptor from a human B cell line. Tandem mass spectrometry of receptor peptides yielded partial amino acid sequences that allowed the identification of corresponding cDNA clones. Sequence analysis of this receptor indicated that it is a novel member of the plexin family and identified a semaphorin-like domain within this family, thus suggesting an evolutionary relationship between receptor and ligand. A39R up-regulated ICAM-1 on, and induced cytokine production from, human monocytes. These data, then, describe a receptor for an immunologically active semaphorin and suggest that it may serve as a prototype for other plexin-semaphorin binding pairs.

Poxvirus semaphorin A39R inhibits phagocytosis by dendritic cells and neutrophils

“…In particular, Plexin C1 is expressed on DC and neutrophils (Walzer et al, in press). Plexin C1 was shown to be the cellular receptor for the poxvirus semaphorin A39R [11]. Our previous results showed that, as in neurons, Plexin C1 engagement by A39R semaphorin on mouse DC induces local actin cytoskeleton rearrangement and inhibits integrin-mediated adhesion (Walzer et al, in press).…”

“…All of the experimental procedures used in this study were approved by a local committee according to federal guidelines. SFHA39R (Shorty-Flag-Histidine, referred as A39R in the text) was expressed in Chinese hamster ovary (CHO) cells and purified as previously described [11]. All proteins were tested for endotoxin content using a Limulus assay (Whittaker M. A. Bioproducts, Walkersville, MD) and were shown to be <3 endotoxin units/mg.…”

“…Plexins are type-I transmembrane proteins that also contain a sema domain in their extracellular part [11,12]. They are divided into four subfamilies, plexins A to D, according to the structure of their extracellular domain.…”

The brain within the tumor: new roles for axon guidance molecules in cancers

“…Both were found to bind to plexin-C1. 20,84 However, recent data suggest that in the nervous system integrins and in particular those containing the b1 subunit, are functional receptors for Sema7A. 85 A possible function of SEMA7A in cancer is unknown.…”

MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

“…Plexins form a large family of transmembrane proteins, members of which function as co-receptors for both secreted and membrane-associated semaphorins (Fujisawa, 2004;Puschel, 2002;Tamagnone and Comoglio, 2000). Semaphorins bind either directly to plexins or activate plexin-dependent signaling by associating with ligandbinding subunits such as neuropilin proteins (Comeau et al, 1998;Rohm et al, 2000;Takahashi et al, 1999;Tamagnone et al, 1999;Winberg et al, 1998). Following ligand engagement, the plexin cytoplasmic region activates poorly understood downstream signaling pathways, leading to modifications of the growth cone cytoskeleton and axon repulsion (Pasterkamp, 2005;Pasterkamp and Kolodkin, 2003).…”