Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin

Sergey Akimov, Dmitry Krylov, Laurie F. Fleischmana, Alexey M. Belkin

Research output: Contribution to journalArticle

Abstract

The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.

Original languageEnglish (US)
Pages (from-to)825-838
Number of pages14
JournalJournal of Cell Biology
Volume148
Issue number4
DOIs
StatePublished - Feb 21 2000
Externally publishedYes

Fingerprint

Fibronectins
Integrins
Transglutaminases
Focal Adhesions
Cell Adhesion
Factor XIII
Focal Adhesion Protein-Tyrosine Kinases
Gelatin
transglutaminase 2
Adhesives
Catalytic Domain
Phosphorylation
Enzymes
Proteins

Keywords

  • Adhesion
  • Fibronectin
  • Focal adhesions
  • Integrins
  • Tissue transglutaminase

ASJC Scopus subject areas

  • Cell Biology

Cite this

Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin. / Akimov, Sergey; Krylov, Dmitry; Fleischmana, Laurie F.; Belkin, Alexey M.

In: Journal of Cell Biology, Vol. 148, No. 4, 21.02.2000, p. 825-838.

Research output: Contribution to journalArticle

Akimov, Sergey ; Krylov, Dmitry ; Fleischmana, Laurie F. ; Belkin, Alexey M. / Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin. In: Journal of Cell Biology. 2000 ; Vol. 148, No. 4. pp. 825-838.
@article{21086c3d576c436b911f1b43ee1374e4,
title = "Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin",
abstract = "The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.",
keywords = "Adhesion, Fibronectin, Focal adhesions, Integrins, Tissue transglutaminase",
author = "Sergey Akimov and Dmitry Krylov and Fleischmana, {Laurie F.} and Belkin, {Alexey M.}",
year = "2000",
month = "2",
day = "21",
doi = "10.1083/jcb.148.4.825",
language = "English (US)",
volume = "148",
pages = "825--838",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin

AU - Akimov, Sergey

AU - Krylov, Dmitry

AU - Fleischmana, Laurie F.

AU - Belkin, Alexey M.

PY - 2000/2/21

Y1 - 2000/2/21

N2 - The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.

AB - The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading.

KW - Adhesion

KW - Fibronectin

KW - Focal adhesions

KW - Integrins

KW - Tissue transglutaminase

UR - http://www.scopus.com/inward/record.url?scp=0034695929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034695929&partnerID=8YFLogxK

U2 - 10.1083/jcb.148.4.825

DO - 10.1083/jcb.148.4.825

M3 - Article

VL - 148

SP - 825

EP - 838

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 4

ER -