Integrin Structure, Activation, and Interactions

Campbell, Iain D.; Humphries, Martin J.

doi:10.1101/cshperspect.a004994

Cited by 929 publications

(855 citation statements)

References 93 publications

Supporting

Mentioning

842

Contrasting

Unclassified

Order By: Relevance

“…Subgroups of integrins are defined by binding to collagens, laminins, or RGD amino acid sequences, or by being expressed on leukocytes. Integrin structure and function are discussed elsewhere in this collection and in several reviews (Hynes 2002;Luo et al 2007;Askari et al 2009;Geiger et al 2009;Campbell and Humphries 2011;Wickstrom et al 2011;Geiger and Yamada 2011).…”

Section: Cross Talk Between Integrins and Growth Factorsmentioning

confidence: 99%

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Munger¹,

Sheppard²

2011

Cold Spring Harbor Perspectives in Biology

326

275

View full text Add to dashboard Cite

The growth factor TGF-b is secreted in a latent complex consisting of three proteins: TGF-b, an inhibitor (latency-associated protein, LAP, which is derived from the TGF-b propeptide) and an ECM-binding protein (one of the latent TGF-b binding proteins, or LTBPs). LTBPs interact with fibrillins and other ECM components and thus function to localize latent TGF-b in the ECM. LAP contains an integrin-binding site (RGD), and several RGD-binding integrins are able to activate latent TGF-b through binding this site. Mutant mice defective in integrin-mediated activators, and humans and mice with fibrillin gene mutations, show the critical role of ECM and integrins in regulating TGF-b signaling.

show abstract

Section: Cross Talk Between Integrins and Growth Factorsmentioning

confidence: 99%

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Munger¹,

Sheppard²

2011

Cold Spring Harbor Perspectives in Biology

326

275

View full text Add to dashboard Cite

show abstract

“…To fulfill these duties, integrin assembly constitutes obligate noncovalently-bound heterodimers (8). At least 18 a-and 8 b-subunits have been identified in mammals, which generate 24 distinct integrins.…”

Section: Integrin Physiognomymentioning

confidence: 99%

Integrin Regulation during Leukocyte Recruitment

Herter

Zarbock

2013

The Journal of Immunology

170

138

View full text Add to dashboard Cite

Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. In this review, we discuss the different signaling pathways leading to the change of integrin adhesiveness in neutrophils, monocytes, and lymphocytes. We thereby focus on the importance of integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration, as each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. Additionally, we discuss endogenous mechanisms that balance and counteract integrin activation and limit leukocyte recruitment at the site of inflammation. Further insight into these complex mechanisms may provide new approaches for developing new anti-inflammatory therapies.

show abstract

“…Dynamic remodeling of the ECM through regulated deposition, assembly, and degradation is critical for all ECM functions. ECM exerts its influence on surrounding cells through its interaction with matrix-sensing receptors on the cell surface, such as integrins (Campbell and Humphries 2011), and by regulation of the bioavailability of signaling molecules through regulated sequestration, release, and activation (Hynes 2009). The importance of the ECM to normal development and homeostasis is highlighted by the number of disorders that are either caused or exacerbated by abnormal ECM function (reviewed in Bateman et al 2009;Bonnans et al 2014).…”

Section: Extracellular Matrix -Dependent Regulation Of Tgf-b Bioavailmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

show abstract

Integrin Structure, Activation, and Interactions

Cited by 929 publications

References 93 publications

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Integrin Regulation during Leukocyte Recruitment

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

Contact Info

Product

Resources

About