Tyrosine kinase-dependent activation of human NK cell functions upon triggering through CD44 receptor.
We recently showed evidence of CD44-mediated enhancement of natural killer (NK) cell cytotoxic activity and induction of intracellular Ca2+ flux. In this study, we evaluated whether CD44 plays a stimulatory role in NK cell functions, such as cytokine production and activation antigen expression. Our results indicate that ligation of the CD44 receptor results in the induction of expression of the CD69 surface activation antigen as well as in the enhancement of phorbol ester-induced TNF-alpha secretion. We report also evidence for the coupling of CD44 receptor to a protein tyrosine kinase(s) pathway. CD44 engagement rapidly stimulates the tyrosine phosphorylation of several cellular substrates. Pretreatment of NK cells with the tyrosine kinase inhibitor herbimycin A resulted in marked decrease of CD44-stimulated phosphorylation, indicating that it activates tyrosine kinase(s). Furthermore, the drug also prevents CD44-mediated TNF-alpha production and CD69 expression. These findings indicate that protein tyrosine phosphorylation is an early and critical event in CD44-mediated activation of NK cell functions.
Galandrini
R
R
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Piccoli
M
M
Frati
L
L
Santoni
A
A
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens