MilliporeSigma

SHARPIN is an endogenous inhibitor of β1-integrin activation.

Nature cell biology (2011-09-29)
Juha K Rantala, Jeroen Pouwels, Teijo Pellinen, Stefan Veltel, Petra Laasola, Elina Mattila, Christopher S Potter, Ted Duffy, John P Sundberg, Olli Kallioniemi, Janet A Askari, Martin J Humphries, Maddy Parsons, Marko Salmi, Johanna Ivaska
ABSTRACT

Regulated activation of integrins is critical for cell adhesion, motility and tissue homeostasis. Talin and kindlins activate β1-integrins, but the counteracting inhibiting mechanisms are poorly defined. We identified SHARPIN as an important inactivator of β1-integrins in an RNAi screen. SHARPIN inhibited β1-integrin functions in human cancer cells and primary leukocytes. Fibroblasts, leukocytes and keratinocytes from SHARPIN-deficient mice exhibited increased β1-integrin activity, which was fully rescued by re-expression of SHARPIN. We found that SHARPIN directly binds to a conserved cytoplasmic region of integrin α-subunits and inhibits recruitment of talin and kindlin to the integrin. Therefore, SHARPIN inhibits the critical switching of β1-integrins from inactive to active conformations.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Goat MINUS, Affinity purified Donkey anti-Goat IgG (H+L)
Sigma-Aldrich
Duolink® In Situ Detection Reagents Red
Sigma-Aldrich
Duolink® In Situ Probemaker PLUS
Sigma-Aldrich
Duolink® In Situ Mounting Medium with DAPI
Sigma-Aldrich
Duolink® In Situ Microplate Heat Transfer Block
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Rabbit PLUS, Affinity purified Donkey anti-Rabbit IgG (H+L)
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Mouse MINUS, Affinity purified Donkey anti-Mouse IgG (H+L)
Sigma-Aldrich
Duolink® In Situ Microplate Nuclear Stain, Anti-Fade
Sigma-Aldrich
Duolink® In Situ Wash Buffers, Fluorescence
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Rabbit MINUS
Sigma-Aldrich
Duolink® In Situ Detection Reagents Orange
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Mouse PLUS
Sigma-Aldrich
Duolink® In Situ Probemaker MINUS
Sigma-Aldrich
Duolink® In Situ PLA® Probe Anti-Goat PLUS
Sigma-Aldrich
Duolink® In Situ Detection Reagents Green
Sigma-Aldrich
Duolink® In Situ Detection Reagents FarRed