SHARPIN is an endogenous inhibitor of β1-integrin activation.

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.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Rantala JK,Pouwels J,Pellinen T,Veltel S,Laasola P,Mattila E,Potter CS,Duffy T,Sundberg JP,Kallioniemi O,Askari JA,Humphries MJ,Parsons M,Salmi M,Ivaska J

doi

10.1038/ncb2340

subject

Has Abstract

pub_date

2011-09-25 00:00:00

pages

1315-24

issue

11

eissn

1465-7392

issn

1476-4679

pii

ncb2340

journal_volume

13

pub_type

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