|
|
 Previous Article | Table of Contents | Next Article 
Substitutions and deletions in the cytoplasmic domain of the phagocytic
receptor Fc gamma RIIA: effect on receptor tyrosine phosphorylation and
phagocytosis [published erratum appears in Blood 1994 Nov 1;84(9):3252]
MA Mitchell, MM Huang, P Chien, ZK Indik, XQ Pan and AD Schreiber
Department of Medicine, University of Pennsylvania School of Medicine,
Philadelphia.
Fc gamma RIIA in the absence of other Fc receptors or receptor subunits
induces the ingestion of IgG-coated cells. The cytoplasmic domain of Fc
gamma RIIA contains two Y-x-x-L sequences similar to those in other Ig gene
family receptors plus an additional tyrosine residue not in a Y-x- x-L
motif. Upon cross-linking, Fc gamma RIIA is phosphorylated on tyrosine and
the cytoplasmic tyrosines, Y275 (Y1), Y282 (Y2), and Y298 (Y3), may be
important for its phagocytic activity. Because COS-1 cells can serve as a
model for examining molecular structures involved in phagocytosis,
substitutions and deletions were introduced into the cytoplasmic domain of
Fc gamma RIIA and examined in COS-1 cell transfectants for their effects on
phagocytosis and tyrosine phosphorylation. Disruption of a single
cytoplasmic Y-x-x-L motif by substitution of tyrosine Y2 or Y3 by
phenylalanine or by removing the threonine and leucine residues within the
motif inhibited phagocytosis 50% to 65%. Tyrosine phosphorylation of Fc
gamma RIIA also was inhibited, although to a greater extent by the
substitution of Y3 than of Y2. Replacement of the N-terminal first
cytoplasmic domain tyrosine, Y1, which is not within a typical Y-x-x-L, by
itself did not inhibit phagocytosis, but replacement of Y1 in mutants
lacking Y2 or Y3 virtually eliminated phagocytic activity and receptor
tyrosine phosphorylation. Thus, at least two cytoplasmic tyrosines,
including at least one typical single Y-x-x-L motif, are required for
phagocytosis by Fc gamma RIIA. The data suggest that there is a close but
not a simple relationship between phosphorylation of the Fc gamma RIIA
cytoplasmic tyrosines and Fc gamma RIIA-mediated phagocytosis. Y3 appears
to be particularly important because its removal by truncation or
replacement with phenylalanine inhibits both tyrosine phosphorylation and
phagocytosis in parallel. Alterations in the 12 residue proline-containing
sequence between the two Y-x-x-L motifs also reduced phagocytic activity
and tyrosine phosphorylation. Thus, the specific structure of the Fc gamma
RIIA cytoplasmic domain accounts for its ability to stimulate phagocytosis
in the absence of other subunits.
Volume 84,
Issue 6,
pp. 1753-1759,
09/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Z.-Y. Huang, D. R. Barreda, R. G. Worth, Z. K. Indik, M.-K. Kim, P. Chien, and A. D. Schreiber
Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis
J. Leukoc. Biol.,
December 1, 2006;
80(6):
1553 - 1562.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. W. S. I. Rodrigo, X. Jin, S. D. Blackley, R. C. Rose, and J. J. Schlesinger
Differential Enhancement of Dengue Virus Immune Complex Infectivity Mediated by Signaling-Competent and Signaling-Incompetent Human Fc{gamma}RIA (CD64) or Fc{gamma}RIIA (CD32).
J. Virol.,
October 1, 2006;
80(20):
10128 - 10138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Leopold, R. L. Wendland, T. Vincent, and R. G. Crystal
Neutralized Adenovirus-Immune Complexes Can Mediate Effective Gene Transfer via an Fc Receptor-Dependent Infection Pathway.
J. Virol.,
October 1, 2006;
80(20):
10237 - 10247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Cougoule, S. Hoshino, A. Dart, J. Lim, and E. Caron
Dissociation of Recruitment and Activation of the Small G-protein Rac during Fc{gamma} Receptor-mediated Phagocytosis
J. Biol. Chem.,
March 31, 2006;
281(13):
8756 - 8764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sobota, A. Strzelecka-Kiliszek, E. Gladkowska, K. Yoshida, K. Mrozinska, and K. Kwiatkowska
Binding of IgG-Opsonized Particles to Fc{gamma}R Is an Active Stage of Phagocytosis That Involves Receptor Clustering and Phosphorylation
J. Immunol.,
October 1, 2005;
175(7):
4450 - 4457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Herre, A. S. J. Marshall, E. Caron, A. D. Edwards, D. L. Williams, E. Schweighoffer, V. Tybulewicz, C. R. e Sousa, S. Gordon, and G. D. Brown
Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages
Blood,
December 15, 2004;
104(13):
4038 - 4045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-Y. Huang, S. Hunter, M.-K. Kim, P. Chien, R. G. Worth, Z. K. Indik, and A. D. Schreiber
The monocyte Fc{gamma} receptors Fc{gamma}RI/{gamma} and Fc{gamma}RIIA differ in their interaction with Syk and with Src-related tyrosine kinases
J. Leukoc. Biol.,
August 1, 2004;
76(2):
491 - 499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. F. Rosse, P. Hillmen, and A. D. Schreiber
Immune-Mediated Hemolytic Anemia
Hematology,
January 1, 2004;
2004(1):
48 - 62.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. P. Ganesan, H. Fang, C. B. Marsh, and S. Tridandapani
The Protein-tyrosine Phosphatase SHP-1 Associates with the Phosphorylated Immunoreceptor Tyrosine-based Activation Motif of Fc{gamma}RIIa to Modulate Signaling Events in Myeloid Cells
J. Biol. Chem.,
September 12, 2003;
278(37):
35710 - 35717.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-K. Kim, Z.-Y. Huang, P.-H. Hwang, B. A. Jones, N. Sato, S. Hunter, T.-H. Kim-Han, R. G. Worth, Z. K. Indik, and A. D. Schreiber
Fc{gamma} receptor transmembrane domains: role in cell surface expression, {gamma} chain interaction, and phagocytosis
Blood,
June 1, 2003;
101(11):
4479 - 4484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Worth, M.-K. Kim, A. L. Kindzelskii, H. R. Petty, and A. D. Schreiber
Signal sequence within Fcgamma RIIA controls calcium wave propagation patterns: Apparent role in phagolysosome fusion
PNAS,
April 15, 2003;
100(8):
4533 - 4538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kwiatkowska, J. Frey, and A. Sobota
Phosphorylation of Fc{gamma}RIIA is required for the receptor-induced actin rearrangement and capping: the role of membrane rafts
J. Cell Sci.,
February 1, 2003;
116(3):
537 - 550.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Strzelecka-Kiliszek, K. Kwiatkowska, and A. Sobota
Lyn and Syk Kinases Are Sequentially Engaged in Phagocytosis Mediated by Fc{gamma}R
J. Immunol.,
December 15, 2002;
169(12):
6787 - 6794.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Barabe, E. Rollet-Labelle, C. Gilbert, M. J. G. Fernandes, S. N. Naccache, and P. H. Naccache
Early Events in the Activation of Fc{gamma}RIIA in Human Neutrophils: Stimulated Insolubilization, Translocation to Detergent-Resistant Domains, and Degradation of Fc{gamma}RIIA
J. Immunol.,
April 15, 2002;
168(8):
4042 - 4049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Worth, L. Mayo-Bond, M.-K. Kim, J. G. J. van de Winkel, R. F. Todd III, H. R. Petty, and A. D. Schreiber
The cytoplasmic domain of Fcgamma RIIA (CD32) participates in phagolysosome formation
Blood,
December 1, 2001;
98(12):
3429 - 3434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gilbert, F. Barabe, E. Rollet-Labelle, S. G. Bourgoin, S. R. McColl, B. B. Damaj, and P. H. Naccache
Evidence for a Role for SAM68 in the Responses of Human Neutrophils to Ligation of CD32 and to Monosodium Urate Crystals
J. Immunol.,
April 1, 2001;
166(7):
4664 - 4671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Edberg, A. M. F. Yee, D. S. Rakshit, D. J. Chang, J. A. Gokhale, Z. K. Indik, A. D. Schreiber, and R. P. Kimberly
The Cytoplasmic Domain of Human Fcgamma RIa Alters the Functional Properties of the Fcgamma RI{middle dot}gamma -Chain Receptor Complex
J. Biol. Chem.,
October 15, 1999;
274(42):
30328 - 30333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. P. Downey, R. J. Botelho, J. R. Butler, Y. Moltyaner, P. Chien, A. D. Schreiber, and S. Grinstein
Phagosomal Maturation, Acidification, and Inhibition of Bacterial Growth in Nonphagocytic Cells Transfected with Fcgamma RIIA Receptors
J. Biol. Chem.,
October 1, 1999;
274(40):
28436 - 28444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pricop, J. Gokhale, P. Redecha, S. C. Ng, and J. E. Salmon
Reactive Oxygen Intermediates Enhance Fc{gamma} Receptor Signaling and Amplify Phagocytic Capacity
J. Immunol.,
June 15, 1999;
162(12):
7041 - 7048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hunter, Z. K. Indik, M.-K. Kim, M. D. Cauley, J.-G. Park, and A. D. Schreiber
Inhibition of Fcgamma Receptor-Mediated Phagocytosis by a Nonphagocytic Fcgamma Receptor
Blood,
March 1, 1998;
91(5):
1762 - 1768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Lowry, A.-M. Duchemin, J. M. Robinson, and C. L. Anderson
Functional Separation of Pseudopod Extension and Particle Internalization during Fcgamma Receptor-mediated Phagocytosis
J. Exp. Med.,
January 19, 1998;
187(2):
161 - 176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Green, A. D. Schreiber, and E. J. Brown
Role for a Glycan Phosphoinositol Anchor in Fcgamma Receptor Synergy
J. Cell Biol.,
December 1, 1997;
139(5):
1209 - 1217.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. W. Chacko, J. T. Brandt, K. M. Coggeshall, and C. L. Anderson
Phosphoinositide 3-Kinase and p72[IMAGE] Noncovalently Associate with the Low Affinity Fc[IMAGE] Receptor on Human Platelets through an Immunoreceptor Tyrosine-based Activation Motif
J. Biol. Chem.,
May 3, 1996;
271(18):
10775 - 10781.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Edberg, C.-T. Lin, D. Lau, J. C. Unkeless, and R. P. Kimberly
The Ca[IMAGE] Dependence of Human Fc[IMAGE] Receptor-initiated Phagocytosis
J. Biol. Chem.,
September 22, 1995;
270(38):
22301 - 22307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Zhu, Z. Bao, and J. Li
MacMARCKS Mutation Blocks Macrophage Phagocytosis of Zymosan
J. Biol. Chem.,
July 28, 1995;
270(30):
17652 - 17655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
