The polybasic insertion in autotaxin α confers specific binding to heparin and cell surface heparan sulfate proteoglycans.

ABSTRACT: Autotaxin (ATX) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA), playing a key role in diverse physiological and pathological processes. ATX exists in distinct splice variants, but isoform-specific functions remain elusive. Here we characterize the ATXα isoform, which differs from the canonical form (ATXβ) in having a 52-residue polybasic insertion of unknown function in the catalytic domain. We find that the ATXα insertion is susceptible to cleavage by extracellular furin-like endoproteases, but cleaved ATXα remains structurally and functionally intact due to strong interactions within the catalytic domain. Through ELISA and surface plasmon resonance assays, we show that ATXα binds specifically to heparin with high affinity (K(d) ~10(-8) M),

SUBMITTER: Houben AJ 

PROVIDER: S-EPMC3537048 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature