Research ExplorerPublicationsSHARPIN is an endogenous inhibitor of β1-integrin activation

SHARPIN is an endogenous inhibitor of β1-integrin activation

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SHARPIN is an endogenous inhibitor of β1-integrin activation. / Rantala, Juha K; Pouwels, Jeroen; Pellinen, Teijo; Veltel, Stefan; Laasola, Petra; Mattila, Elina; Potter, Christopher S; Duffy, Ted; Sundberg, John P; Kallioniemi, Olli; Askari, Janet A; Humphries, Martin J; Parsons, Maddy; Salmi, Marko; Ivaska, Johanna.

In: NAT CELL BIOL, Vol. 13, No. 11, 01.11.2011, p. 1315-24.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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 2011, 'SHARPIN is an endogenous inhibitor of β1-integrin activation', NAT CELL BIOL, vol. 13, no. 11, pp. 1315-24. https://doi.org/10.1038/ncb2340

APA

Rantala, J. K., Pouwels, J., Pellinen, T., Veltel, S., Laasola, P., Mattila, E., Potter, C. S., Duffy, T., Sundberg, J. P., Kallioniemi, O., Askari, J. A., Humphries, M. J., Parsons, M., Salmi, M., & Ivaska, J. (2011). SHARPIN is an endogenous inhibitor of β1-integrin activation. NAT CELL BIOL, 13(11), 1315-24. https://doi.org/10.1038/ncb2340

Vancouver

Rantala JK, Pouwels J, Pellinen T, Veltel S, Laasola P, Mattila E et al. SHARPIN is an endogenous inhibitor of β1-integrin activation. NAT CELL BIOL. 2011 Nov 1;13(11):1315-24. https://doi.org/10.1038/ncb2340

Bibtex

@article{2d04a7c521fe487ca8e47d83ea517cbf,
title = "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.",
keywords = "Animals, Antigens, CD29, Binding Sites, Cell Line, Tumor, Cell Movement, Fibroblasts, Humans, Keratinocytes, Leukocytes, Ligands, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Nerve Tissue Proteins, Protein Conformation, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Protein Subunits, RNA Interference, Recombinant Fusion Proteins, Structure-Activity Relationship, Talin, Transfection",
author = "Rantala, {Juha K} and Jeroen Pouwels and Teijo Pellinen and Stefan Veltel and Petra Laasola and Elina Mattila and Potter, {Christopher S} and Ted Duffy and Sundberg, {John P} and Olli Kallioniemi and Askari, {Janet A} and Humphries, {Martin J} and Maddy Parsons and Marko Salmi and Johanna Ivaska",
year = "2011",
month = nov,
day = "1",
doi = "10.1038/ncb2340",
language = "English",
volume = "13",
pages = "1315--24",
journal = "NAT CELL BIOL",
issn = "1465-7392",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - SHARPIN is an endogenous inhibitor of β1-integrin activation

AU - Rantala, Juha K

AU - Pouwels, Jeroen

AU - Pellinen, Teijo

AU - Veltel, Stefan

AU - Laasola, Petra

AU - Mattila, Elina

AU - Potter, Christopher S

AU - Duffy, Ted

AU - Sundberg, John P

AU - Kallioniemi, Olli

AU - Askari, Janet A

AU - Humphries, Martin J

AU - Parsons, Maddy

AU - Salmi, Marko

AU - Ivaska, Johanna

PY - 2011/11/1

Y1 - 2011/11/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD29

KW - Binding Sites

KW - Cell Line, Tumor

KW - Cell Movement

KW - Fibroblasts

KW - Humans

KW - Keratinocytes

KW - Leukocytes

KW - Ligands

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mutation

KW - Nerve Tissue Proteins

KW - Protein Conformation

KW - Protein Interaction Domains and Motifs

KW - Protein Interaction Mapping

KW - Protein Subunits

KW - RNA Interference

KW - Recombinant Fusion Proteins

KW - Structure-Activity Relationship

KW - Talin

KW - Transfection

U2 - 10.1038/ncb2340

DO - 10.1038/ncb2340

M3 - SCORING: Journal article

C2 - 21947080

VL - 13

SP - 1315

EP - 1324

JO - NAT CELL BIOL

JF - NAT CELL BIOL

SN - 1465-7392

IS - 11

ER -