The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction

Blechman, Janna M; Lev, Sima; Barg, Jacob; Eisenstein, Miriam; Vaks, Baruch; Vogel, Zvi; Givol, David; Yarden, Yosef

doi:10.1016/0092-8674(95)90455-7

Cited by 156Receptor Mechanisms and SignalingCytokine Signaling Pathways and InteractionsProtein Kinase Regulation and GTPase Signaling

The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction

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Blechman, Janna M, Lev, Sima, Barg, Jacob, Eisenstein, Miriam, Vaks, Baruch, Vogel, Zvi, Givol, David, Yarden, Yosef·1995·Cell

DOI 10.1016/0092-8674(95)90455-7

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Abstract

Receptor dimerization is ubiquitous to the action of all receptor tyrosine kinases, and in the case of dimeric ligands, such as the stem cell factor (SCF), it was attributed to ligand bivalency. However, by using a dimerization-inhibitory monoclonal antibody to the SCF receptor, we confined a putative dimerization site to the nonstandard fourth immunoglobulin-like domain of the receptor. Deletion of this domain not only abolished ligand-induced dimerization and completely inhibited signal transduction, but also provided insights into the mechanism of the coupling of ligand binding to dimer formation. These results identify an intrinsic receptor dimerization site and suggest that similar sites may exist in other receptors.

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Both mutations affect the fourth Ig domain of KIT, and mutations in this motif near the dimerization site have been shown to result in accelerated ligand dissociation and reduced downstream signal transduction events.
“Both mutations affect the fourth Ig domain of KIT, and mutations in this motif near the dimerization site have been shown to result in accelerated ligand dissociation and reduced downstream signal transduction events (68).”
From Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication (2014) · cites this paper as [68]

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Authors: Blechman, J. M., Lev, S., Barg, J., Eisenstein, M., Vaks, B., Vogel, Z., Givol, D., & Yarden, Y.
Affiliations: Weizmann Institute of Science (IL)
Tel Aviv University (IL)
ORCID: Lev, Sima
Eisenstein, Miriam
Yarden, Yosef
Venue: Cell
Publisher: Elsevier BV
Published: 1995-01
Volume: 80
Issue: 1
Pages: 103-113
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(95)90455-7
OpenAlex: W2054154416
Cited by: 156
References: 37
Citations by year: 2025: 2 · 2024: 1 · 2023: 1 · 2021: 1 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 6 · 2013: 5 · 2012: 1
FWCI: 6.19
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6772 d)
Locations: Cell (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Israel Cancer Research Fund
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: CD117, receptor dimerization, ligand binding, signal transduction, receptor tyrosine kinase, domain deletion
MeSH terms: Animals, Antibodies, Monoclonal, Base Sequence, Binding Sites, Cells, Cultured, Enzyme Activation, Humans, Ligands, Models, Molecular, Molecular Sequence Data, Mutation, Proto-Oncogene Proteins, Solubility, Signal Transduction, Receptors, Colony-Stimulating Factor, Hematopoietic Cell Growth Factors, Epitope Mapping, Proto-Oncogene Proteins c-kit, Stem Cell Factor, Receptor Protein-Tyrosine Kinases, Mice

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The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction

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