Intact signal peptide of CD18, the beta-subunit of beta2-integrins, renders ruminants susceptible to Mannheimia haemolytica leukotoxin.

ABSTRACT: Signal peptides of membrane proteins are cleaved by endoplasmic reticulum-resident signal peptidase, and thus, are not present on mature membrane proteins. Here, we report that, contrary to the paradigm, the signal peptide of ruminant CD18, the beta-subunit of beta(2)-integrins, is not cleaved. Intriguingly, the intact signal peptide of CD18 is responsible for the susceptibility of ruminant leukocytes to Mannheimia (Pasteurella) haemolytica leukotoxin (Lkt). Inhibition of Lkt-induced cytolysis of ruminant leukocytes by CD18 peptide analogs revealed that the Lkt-binding site is formed by amino acids 5-17 of CD18, which, surprisingly, comprise most of the signal sequence. Flow cytometric analysis of ruminant leukocytes indicated the presence of the signal peptide on mature CD18 molecules exp

SUBMITTER: Shanthalingam S 

PROVIDER: S-EPMC2741271 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature