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
-
- Animals
- Human Umbilical Vein Endothelial Cells
- Humans
- Integrin beta1/genetics
- Integrin beta1/metabolism*
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Neoplasm Proteins/genetics
- Neoplasm Proteins/metabolism*
- Protein Structure, Tertiary
- Signal Transduction/physiology*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 24599960 Full text @ J. Biol. Chem.
Citation
Fitzpatrick, P., Shattil, S.J., Ablooglu, A.J. (2014) C-terminal COOH of Integrin beta1 Is Necessary for beta1 Association with the Kindlin-2 Adapter Protein. The Journal of biological chemistry. 289:11183-93.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping