Structural requirements of Syk kinase for Fcgamma receptor-mediated phagocytosis.
The tyrosine kinase Syk plays a critical role in the phagocytic pathway mediated by Fcgamma receptors (FcgammaR). In transfected COS1 cells co-expression of Syk enhances FcgammaR mediated phagocytosis. The other member of the Syk kinase family, the highly homologous tyrosine kinase Zap70, also plays a role in signaling by immunoglobulin gene family receptors, but does not increase the phagocytic efficiency of FcgammaRs. The homologous tandem SH2 and kinase domains of Syk and Zap70 are separated by a nonhomologous region referred to as the unique domain. Zap70's inability to enhance phagocytosis was not due to unique domain tyrosine 292, previously implicated in negative regulation of Zap70 function. We determined the regions of Syk important for its interaction with the phagocytic pathway. An intact kinase domain was required for Syk's effect on phagocytosis. Furthermore, the Syk variant SykB, lacking 23 amino acids in the unique region, signaled for phagocytosis as efficiently as did Syk. We then constructed exchange chimeras between Syk and Zap70 and determined the contributions of the SH2, unique and kinase domains to phagocytic signaling. Our data suggest that the Syk kinase domain, which has high intrinsic kinase activity, is important for facilitating phagocytic signaling by FcgammaRI and FcgammaRIIIA.
Hunter
S
S
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. Shunter@mail.med.upenn.edu
Sato
N
N
Kim
M K
MK
Huang
Z Y
ZY
Chu
D H
DH
Park
J G
JG
Schreiber
A D
AD
D000818:Animals; D019556:COS Cells; D004792:Enzyme Precursors / Q000737:chemistry / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D010587:Phagocytosis / Q000502:physiology*; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology*; D017452:Receptors, IgG / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase