Lipoarabinomannans activate the protein tyrosine kinase hck in human neutrophils

The mycobacterial lipoarabinomannans (LAMs) are glycosylphosphatidyl-myo-in ositol-anchored lipoglycans with diverse biological activities. It has been shown that purified LAMs interact directly, or indirectly, through recepto rs with the plasma membrane receptors of target cells located in domains ri ch in glycosylphosphatidylinositol-anchored proteins that contain Src famil y protein tyrosine kinases. To examine whether LAMs could activate Src-rela ted kinases, human neutrophils were exposed to mannosylated LAMs (ManLAMs) purified from the vaccinal strain Mycobacterium bovis BCG and to phosphoino sitol-capped LAMs (AraLAM or PILAM) obtained from the nonpathogenic species Mycobacterium smegmatis. We report first that both ManLAMs and PILAMs acti vate Hck in a rapid and transient manner and second that complete deacylati on of ManLAM abolished its effect on Hck activity, thereby demonstrating th at acylation of LAM but not mannosylation is critical for Hck activation. T hese data indicate that Hck is involved in the signaling pathway of LAMs, m olecules known for their ability to trigger several responses in eukaryotic cells.