Lipoarabinomannans activate the protein tyrosine kinase Hck in human neutrophils.
The mycobacterial lipoarabinomannans (LAMs) are glycosylphosphatidyl-myo-inositol-anchored lipoglycans with diverse biological activities. It has been shown that purified LAMs interact directly, or indirectly, through receptors with the plasma membrane receptors of target cells located in domains rich in glycosylphosphatidylinositol-anchored proteins that contain Src family protein tyrosine kinases. To examine whether LAMs could activate Src-related kinases, human neutrophils were exposed to mannosylated LAMs (ManLAMs) purified from the vaccinal strain Mycobacterium bovis BCG and to phosphoinositol-capped LAMs (AraLAM or PILAM) obtained from the nonpathogenic species Mycobacterium smegmatis. We report first that both ManLAMs and PILAMs activate Hck in a rapid and transient manner and second that complete deacylation of ManLAM abolished its effect on Hck activity, thereby demonstrating that acylation of LAM but not mannosylation is critical for Hck activation. These data indicate that Hck is involved in the signaling pathway of LAMs, molecules known for their ability to trigger several responses in eukaryotic cells.
Astarie-Dequeker
C
C
Institut de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, 31077 Toulouse, France.
Nigou
J
J
Puzo
G
G
Maridonneau-Parini
I
I
D000215:Acylation; D004789:Enzyme Activation; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology*; D008351:Mannans / Q000737:chemistry / Q000494:pharmacology; D009161:Mycobacterium / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D020102:Mycobacterium smegmatis / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases / Q000378:metabolism*
D008070:Lipopolysaccharides; D008351:Mannans; D011518:Proto-Oncogene Proteins; C050016:lipoarabinomannan; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases