en
Scientific article
English

Dimerization of Kit-ligand and efficient cell-surface presentation requires a conserved Ser-Gly-Gly-Tyr motif in its transmembrane domain

Published inThe FASEB journal, vol. 23, no. 9, p. 3037-3048
Publication date2009
Abstract

Kit-ligand (Kitl), also known as stem cell factor, is a membrane-anchored, noncovalently bound dimer signaling via the c-kit receptor tyrosine kinase, required for migration, survival, and proliferation of hematopoietic stem and germ cells, melanocytes, and mastocytes. Despite its fundamental role in morphogenesis and stem cell biology, the mechanisms that regulate Kitl dimerization are not well understood. By employing cell-permeable cross-linker and quantitative bimolecular fluorescence complementation of wild-type and truncated forms of Kitl, we determined that Kitl dimerization is initiated in the endoplasmic reticulum and mediated to similar levels by the transmembrane and the extracellular growth factor domain. Further biochemical and mutational analysis revealed a conserved Ser-Gly-Gly-Tyr-containing motif that is required for transmembrane domain dimerization and efficient cell-surface expression of Kitl. A novel intracellular capture assay with the Kitl transmembrane domain as bait revealed specific interactions with Kitl, but not with unrelated transmembrane proteins. During evolution, the transmembrane dimerization motif appeared in Kitl at the transition from teleosts to tetrapods, which correlates with the emergence of Kitl as a supporter of stem cell populations. Thus, transmembrane-mediated association of membrane-anchored growth factors consists of a novel mechanism to improve paracrine signaling and morphogenesis.

Keywords
  • Amino Acid Motifs
  • Animals
  • COS Cells
  • Cell Line
  • Cell Membrane/ metabolism
  • Cercopithecus aethiops
  • Conserved Sequence
  • Dogs
  • Membrane Proteins/chemistry
  • Mice
  • Protein Multimerization
  • Stem Cell Factor/ chemistry
Citation (ISO format)
PAULHE, Frédérique et al. Dimerization of Kit-ligand and efficient cell-surface presentation requires a conserved Ser-Gly-Gly-Tyr motif in its transmembrane domain. In: The FASEB journal, 2009, vol. 23, n° 9, p. 3037–3048. doi: 10.1096/fj.09-129577
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0892-6638
548views
0downloads

Technical informations

Creation08/27/2010 1:35:47 PM
First validation08/27/2010 1:35:47 PM
Update time03/14/2023 4:04:48 PM
Status update03/14/2023 4:04:48 PM
Last indexation02/12/2024 7:22:28 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack