PUBLICATION

C-terminal COOH of Integrin beta1 Is Necessary for beta1 Association with the Kindlin-2 Adapter Protein

Authors
Fitzpatrick, P., Shattil, S.J., Ablooglu, A.J.
ID
ZDB-PUB-140513-402
Date
2014
Source
The Journal of biological chemistry   289: 11183-93 (Journal)
Registered Authors
Ablooglu, Ararat
Keywords
Cell-Cell Interaction, Development, FERM, Integrins, Kindlin, PDZ, Protein-Protein Interactions, Zebrafish, cd29, cd51
MeSH Terms
  • Protein Structure, Tertiary
  • Integrin beta1/genetics
  • Integrin beta1/metabolism*
  • Humans
  • Neoplasm Proteins/genetics
  • Neoplasm Proteins/metabolism*
  • Animals
  • Signal Transduction/physiology*
  • Human Umbilical Vein Endothelial Cells
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
(all 16)
PubMed
24599960 Full text @ J. Biol. Chem.
Abstract
Protein-protein interactions are driving forces in cellular processes. As a prime example, transmembrane integrins link extracellular matrix and intracellular proteins, resulting in bidirectional signaling that regulates cell migration, proliferation, differentiation, and survival. Here we provide the first evidence that interaction between the integrin β1 cytoplasmic tail and kindlin-2, a member of a family of adapters implicated in human disease pathogenesis, is mainly governed by the β1 C-terminal carboxylate moiety and is required for laterality organ development in zebrafish. Affinity measurements indicate that this unusual protein-protein interaction mode is coordinated by a putative carboxylate-binding motif in the kindlin-2 FERM subdomain F3. Contrary to the C terminus of proteins that engage PDZ domains, the C-terminal three residues of β1, per se, do not contribute to kindlin-2 binding or to laterality organ development. Thus, by employing zebrafish as an in situ physiological tool to correlate protein structure and function, we have discovered an unexpected association chemistry between an integrin and a key adapter involved in integrin signaling.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ha01TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    fermt2MO1-fermt2MRPHLNO
    fermt2MO2-fermt2MRPHLNO
    itgavMO1-itgavMRPHLNO
    itgb1bMO2-itgb1bMRPHLNO
    1 - 4 of 4
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    Fish
    Antibodies
    Orthology
    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
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    Mapping