Medical College of Wisconsin
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Tyrosine phosphorylation of integrin beta3 regulates kindlin-2 binding and integrin activation. J Biol Chem 2010 Oct 01;285(40):30370-4

Date

08/13/2010

Pubmed ID

20702409

Pubmed Central ID

PMC2945529

DOI

10.1074/jbc.C110.134247

Scopus ID

2-s2.0-77957269801 (requires institutional sign-in at Scopus site)   48 Citations

Abstract

Kindlins are essential for integrin activation in cell systems and do so by working in a cooperative fashion with talin via their direct interaction with integrin β cytoplasmic tails (CTs). Kindlins interact with the membrane-distal NxxY motif, which is distinct from the talin-binding site within the membrane-proximal NxxY motif. The Tyr residues in both motifs can be phosphorylated, and it has been suggested that this modification of the membrane-proximal NxxY motif negatively regulates interaction with the talin head domain. However, the influence of Tyr phosphorylation of the membrane-distal NxxY motif on kindlin binding is unknown. Using mutational analyses and phosphorylated peptides, we show that phosphorylation of the membrane-distal NITY(759) motif in the β(3) CT disrupts kindlin-2 recognition. Phosphorylation of this membrane-distal Tyr also disables the ability of kindlin-2 to coactivate the integrin. In direct binding studies, peptides corresponding to the non-phosphorylated β(3) CT interacted well with kindlin-2, whereas the Tyr(759)-phosphorylated peptide failed to bind kindlin-2 with measurable affinity. These observations indicate that transitions between the phosphorylated and non-phosphorylated states of the integrin β(3) CT determine reactivity with kindlin-2 and govern the role of kindlin-2 in regulating integrin activation.

Author List

Bledzka K, Bialkowska K, Nie H, Qin J, Byzova T, Wu C, Plow EF, Ma YQ

Author

Yan-Qing Ma PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Motifs
Humans
Integrin beta3
Membrane Proteins
Neoplasm Proteins
Phosphorylation
Protein Binding
Protein Structure, Tertiary
Tyrosine