Differential activation of the tyrosine kinases ZAP-70 and Syk after Fc gamma RI stimulation.
Engagement of the high-affinity IgG Fc receptor (Fc gamma RI) activates a signal transduction pathway involving tyrosine phosphorylation of associated kinases. We compared the activation of the related protein tyrosine kinases (PTKs), Syk and ZAP-70, in Fc gamma RI-mediated signaling. Cross-linking of the Fc gamma RI multimeric receptor in monocytic cells results in tyrosine phosphorylation of the Fc epsilon RI gamma subunit and association of Syk with this complex. We stably introduced ZAP-70 via a retroviral vector into two monocytic cell lines, U937 and THP-1, which normally do not express ZAP-70. Neither Syk nor MAP kinase activation was affected by the presence of ZAP-70. Although transduced ZAP-70 had in vitro kinase activity and associated with Fc epsilon RI gamma after receptor aggregation, it was not tyrosine phosphorylated. In contrast, both ZAP-70 and Syk were phosphorylated in a T-cell line in which their respective levels of expression were similar to those detected in U937/ZAP-70 cells. Therefore, these results suggest that requirements for Syk and ZAP-70 phosphorylation are distinct in a monocytic cell context.
Taylor
N
N
Division of Research Immunology, Childrens Hospital Los Angeles, CA, USA.
Jahn
T
T
Smith
S
S
Lamkin
T
T
Uribe
L
L
Liu
Y
Y
Durden
D L
DL
Weinberg
K
K
D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human