Differential interaction of Crkl with Cbl or C3G, Hef-1, and γ subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (FcγRI)

Wade T. Kyono, Ron De Jong, Rae Kil Park, Yenbou Liu, Nora Heisterkamp, John Groffen, Donald L. Durden

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cbl-Crkl and Crkl-C3G interactions have been implicated in T cell and B cell receptor signaling and in the regulation of the small GTPase, Rap1. Recent evidence suggests that Rap1 plays a prominent role in the regulation of immunoreceptor tyrosine-based activation motif (ITAM) signaling. To gain insight into the role of Crkl in myeloid ITAM signaling, we investigated Cbl- Crkl and Crkl-C3G interactions following FcγRI aggregation in U937IF cells. FcγRI cross-linking of U937IF cells results in the tyrosine phosphorylation of Cbl, Crkl, and Hef-1, an increase in the association of Crkl with Cbl via direct SH2 domain interaction and increased Crkl-Hef-1 binding. Crkl constitutively binds to the guanine nucleotide-releasing protein, C3G, via direct SH3 domain binding. Our data show that distinct Cbl-Crkl and Crkl-C3G complexes exist in myeloid cells, suggesting that these complexes may modulate distinct signaling events. Anti-Crkl immunoprecipitations demonstrate that the ITAM-containing γ, subunit of FcγRI is induced to form a complex with the Crkl protein, and Crkl binds to the cytoskeletal protein, Hef-1. The induced association of Crkl with Cbl, Hef-1, and FcγRIγ after FcγRI activation and the constitutive association between C3G and Crkl provide the first evidence that a FcγRIγ-Crkl-C3G complex may link ITAM receptors to the activation of Rap1 in myeloid cells.

Original languageEnglish (US)
Pages (from-to)5555-5563
Number of pages9
JournalJournal of Immunology
Volume161
Issue number10
StatePublished - Nov 15 1998

Fingerprint

Immunoreceptor Tyrosine-Based Activation Motif
Fc Receptors
Immunoglobulin G
src Homology Domains
Myeloid Cells
Guanine Nucleotide-Releasing Factor 2
Receptor Aggregation
Cytoskeletal Proteins
Guanine Nucleotides
Monomeric GTP-Binding Proteins
Immunoprecipitation
Tyrosine
B-Lymphocytes
Phosphorylation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Differential interaction of Crkl with Cbl or C3G, Hef-1, and γ subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (FcγRI). / Kyono, Wade T.; De Jong, Ron; Park, Rae Kil; Liu, Yenbou; Heisterkamp, Nora; Groffen, John; Durden, Donald L.

In: Journal of Immunology, Vol. 161, No. 10, 15.11.1998, p. 5555-5563.

Research output: Contribution to journalArticle

Kyono, Wade T. ; De Jong, Ron ; Park, Rae Kil ; Liu, Yenbou ; Heisterkamp, Nora ; Groffen, John ; Durden, Donald L. / Differential interaction of Crkl with Cbl or C3G, Hef-1, and γ subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (FcγRI). In: Journal of Immunology. 1998 ; Vol. 161, No. 10. pp. 5555-5563.
@article{9e3cefd8e57b4ec1917664c7672da620,
title = "Differential interaction of Crkl with Cbl or C3G, Hef-1, and γ subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (FcγRI)",
abstract = "Cbl-Crkl and Crkl-C3G interactions have been implicated in T cell and B cell receptor signaling and in the regulation of the small GTPase, Rap1. Recent evidence suggests that Rap1 plays a prominent role in the regulation of immunoreceptor tyrosine-based activation motif (ITAM) signaling. To gain insight into the role of Crkl in myeloid ITAM signaling, we investigated Cbl- Crkl and Crkl-C3G interactions following FcγRI aggregation in U937IF cells. FcγRI cross-linking of U937IF cells results in the tyrosine phosphorylation of Cbl, Crkl, and Hef-1, an increase in the association of Crkl with Cbl via direct SH2 domain interaction and increased Crkl-Hef-1 binding. Crkl constitutively binds to the guanine nucleotide-releasing protein, C3G, via direct SH3 domain binding. Our data show that distinct Cbl-Crkl and Crkl-C3G complexes exist in myeloid cells, suggesting that these complexes may modulate distinct signaling events. Anti-Crkl immunoprecipitations demonstrate that the ITAM-containing γ, subunit of FcγRI is induced to form a complex with the Crkl protein, and Crkl binds to the cytoskeletal protein, Hef-1. The induced association of Crkl with Cbl, Hef-1, and FcγRIγ after FcγRI activation and the constitutive association between C3G and Crkl provide the first evidence that a FcγRIγ-Crkl-C3G complex may link ITAM receptors to the activation of Rap1 in myeloid cells.",
author = "Kyono, {Wade T.} and {De Jong}, Ron and Park, {Rae Kil} and Yenbou Liu and Nora Heisterkamp and John Groffen and Durden, {Donald L.}",
year = "1998",
month = "11",
day = "15",
language = "English (US)",
volume = "161",
pages = "5555--5563",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Differential interaction of Crkl with Cbl or C3G, Hef-1, and γ subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (FcγRI)

AU - Kyono, Wade T.

AU - De Jong, Ron

AU - Park, Rae Kil

AU - Liu, Yenbou

AU - Heisterkamp, Nora

AU - Groffen, John

AU - Durden, Donald L.

PY - 1998/11/15

Y1 - 1998/11/15

N2 - Cbl-Crkl and Crkl-C3G interactions have been implicated in T cell and B cell receptor signaling and in the regulation of the small GTPase, Rap1. Recent evidence suggests that Rap1 plays a prominent role in the regulation of immunoreceptor tyrosine-based activation motif (ITAM) signaling. To gain insight into the role of Crkl in myeloid ITAM signaling, we investigated Cbl- Crkl and Crkl-C3G interactions following FcγRI aggregation in U937IF cells. FcγRI cross-linking of U937IF cells results in the tyrosine phosphorylation of Cbl, Crkl, and Hef-1, an increase in the association of Crkl with Cbl via direct SH2 domain interaction and increased Crkl-Hef-1 binding. Crkl constitutively binds to the guanine nucleotide-releasing protein, C3G, via direct SH3 domain binding. Our data show that distinct Cbl-Crkl and Crkl-C3G complexes exist in myeloid cells, suggesting that these complexes may modulate distinct signaling events. Anti-Crkl immunoprecipitations demonstrate that the ITAM-containing γ, subunit of FcγRI is induced to form a complex with the Crkl protein, and Crkl binds to the cytoskeletal protein, Hef-1. The induced association of Crkl with Cbl, Hef-1, and FcγRIγ after FcγRI activation and the constitutive association between C3G and Crkl provide the first evidence that a FcγRIγ-Crkl-C3G complex may link ITAM receptors to the activation of Rap1 in myeloid cells.

AB - Cbl-Crkl and Crkl-C3G interactions have been implicated in T cell and B cell receptor signaling and in the regulation of the small GTPase, Rap1. Recent evidence suggests that Rap1 plays a prominent role in the regulation of immunoreceptor tyrosine-based activation motif (ITAM) signaling. To gain insight into the role of Crkl in myeloid ITAM signaling, we investigated Cbl- Crkl and Crkl-C3G interactions following FcγRI aggregation in U937IF cells. FcγRI cross-linking of U937IF cells results in the tyrosine phosphorylation of Cbl, Crkl, and Hef-1, an increase in the association of Crkl with Cbl via direct SH2 domain interaction and increased Crkl-Hef-1 binding. Crkl constitutively binds to the guanine nucleotide-releasing protein, C3G, via direct SH3 domain binding. Our data show that distinct Cbl-Crkl and Crkl-C3G complexes exist in myeloid cells, suggesting that these complexes may modulate distinct signaling events. Anti-Crkl immunoprecipitations demonstrate that the ITAM-containing γ, subunit of FcγRI is induced to form a complex with the Crkl protein, and Crkl binds to the cytoskeletal protein, Hef-1. The induced association of Crkl with Cbl, Hef-1, and FcγRIγ after FcγRI activation and the constitutive association between C3G and Crkl provide the first evidence that a FcγRIγ-Crkl-C3G complex may link ITAM receptors to the activation of Rap1 in myeloid cells.

UR - http://www.scopus.com/inward/record.url?scp=0032533490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032533490&partnerID=8YFLogxK

M3 - Article

C2 - 9820532

AN - SCOPUS:0032533490

VL - 161

SP - 5555

EP - 5563

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -