Proteopedia - User contributions [en]

Molecular Playground/IntegrinBeta1

2014-12-03T00:35:47Z

Elizabeth Brooks:

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
Molecular Playground banner: '''"

'''Banner:''' Studying integrin-mediated metastasis ''in vitro''

<Structure load='3VI4' size='350' frame='true' align='right' caption='Integrin Beta 1 Alpha 5' scene='60/609772/Integrinb1alpha5/1' />
==Structure==
Integrins are surface proteins that are comprised of an alpha subunit and a beta subunit to form a functional transmembrane structure. The subunits of the heterodimer each have small cytoplasmic domains for signal transduction within the cell. There are 18 alpha and eight beta subunits in mammals. Different pairs of these alpha and beta subunits uniquely bind to extracellular proteins. Integrins connect the extracellular environment to the inside of a cell by inducing signals that affect cell functions.

The protein structure on the right has the following color coding: Blue-Alpha 5 chain, Red-Beta 1 chain, Grey-SG/19 Fab fragment light chain, Green-SG/19 Fab fragment heavy chain.

==Function==

Integrins are a class of surface proteins that bind to extracellular matrix components and transmit chemical and mechanical cues to internal signaling pathways. Integrin beta 1 binds many proteins when dimerized with an alpha subunit, including <scene name='60/609772/Integrinbeta1_binding_collagen/1'>collagen</scene>, laminin and fibronectin. Integrin adhesion to the extra cellular matrix is key for cell ability to adhere, migrate and proliferate in both 2D and 3D systems. These will eventually form adhesion complexes, which regulate actomyocin polymerization. During migration, cells continually form new focal adhesions at the leading edge of the cell and release adhesion complexes at the back of the cell, enabling forward movement.

Here are the <scene name='60/609772/N-acetyl-d-glucosamine/2'>N-acetyl-d-glucosamine locations!</scene> N-acetyl-D-glucosamine may regulate integrin signaling during cancer cell migration<ref>PMID:19755493</ref>.

[[Image:Integrin.png|200 px|thumb|Fig. 1: Schematic of integrin heterodimers binding to ECM proteins]]

==Integrins and cancer==

Integrins binding to the extracellular matrix provide cells the ability to migrate and remodel the surrounding microenvironment. Integrins are extremely important in cancer metastasis and the progression of solid tumors. Cells bind to extracellular matrix proteins, like<scene name='60/609772/Rgd_bound/2'> peptide RGD (black) on fibronectin</scene>, with integrins to stimulate survival, migration/invasion, and proliferation <ref>PMID:20029421</ref>. Though high expression of integrin beta 1 has been shown to drive primary tumor progression and metastasis, targeting integrins for cancer treatment has seen limited clinical efficacy <ref>PMID:22894137</ref>. These failures stem from differential integrin expression between cancer cells, but new technologies to screen cancer cell populations are being developed to affective therapies on a patient-specific level <ref> Barney LE, Dandley EC, Jansen LE, Reich NG, Mercurio AM, Peyton SR. “A Cell-ECM Screening Method to Predict Breast Cancer Metastasis”. (2014) In Review.</ref>. These technologies will likely allow for more selective treatment and better clinical efficacy for integrin inhibitors.
[[Image:B1_tissue.png|200 px|thumb|Fig. 2: Beta1 integrin expression in a human breast tumor stained in the Peyton Lab. Beta1 integrin (red) is expressed in the tumor cells. DAPI stains the nuclei in blue.]]

==Studying Integrin Beta-1'' in vitro''==

Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins)<ref>PMID:7955174</ref>, and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM<ref>PMID:9105051 </ref>. When beta1 dimerizes with alpha1, it can bind to both collagens I and IV as well as laminins <ref>PMID: 12662928</ref>, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. </scene> These tools are especially useful when microenvironment stiffness<ref>PMID:20939067</ref> or composition<ref>PMID:15183609</ref> are controlled, allowing for examination of the effect of each of these cues on cell phenotype<ref>PMID:8074327</ref> or downstream signaling.

[[Image:231_beta1.png|315 px|thumb|Fig. 3: Beta1 integrin expression in the human breast cancer cell line MDA-MB-231 stained in the Peyton Lab. Beta1 integrin (green) is expressed mainly around the periphery. DAPI stains the nuclei in blue. Scale bar is 50 microns.]]

==Peyton Lab Research Interests==
The [http://www.peytonlab.org/ Peyton lab] studies how cells process chemical and physical cues from the extracellular matrix and how these interactions play a role in the progression of cardiovascular disease and cancer. We aim to understand the downstream signaling pathways activated when cells use their integrins to bind to matrix and how this translates to the disease of interest. We are further interested in how integrins can be biomarkers in disease, because they transduce signals from the diseased microenvironment to cells, likely facilitating disease progression in some cases.

==References==
<references/>

Molecular Playground/IntegrinBeta1

2014-12-03T00:26:23Z

Elizabeth Brooks:

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
Molecular Playground banner: '''"

'''Banner:''' Studying integrin-mediated metastasis ''in vitro''

<Structure load='3VI4' size='350' frame='true' align='right' caption='Integrin Beta 1 Alpha 5' scene='60/609772/Integrinb1alpha5/1' />
==Structure==
Integrins are surface proteins that are comprised of an alpha subunit and a beta subunit to form a functional transmembrane structure. The subunits of the heterodimer each have small cytoplasmic domains for signal transduction within the cell. Different pairs of alpha and beta subunits uniquely bind to extracellular proteins. Integrins connect the extracellular environment to the inside of a cell to induce signaling within the cell.

The protein structure on the right has the following color coding: Blue-Alpha 5 chain, Red-Beta 1 chain, Grey-SG/19 Fab fragment light chain, Green-SG/19 Fab fragment heavy chain.

==Function==

Integrins are a class of surface proteins that bind to extracellular matrix components and transmit chemical and mechanical cues to internal signaling pathways. Integrin beta 1 binds many proteins when dimerized with an alpha subunit, including <scene name='60/609772/Integrinbeta1_binding_collagen/1'>collagen</scene>, laminin and fibronectin. Integrin adhesion to the extra cellular matrix is key for cell ability to adhere, migrate and proliferate in both 2D and 3D systems. These will eventually form adhesion complexes, which regulate actomyocin polymerization. During migration, cells continually form new focal adhesions at the leading edge of the cell and release adhesion complexes at the back of the cell, enabling forward movement.

Here are the <scene name='60/609772/N-acetyl-d-glucosamine/2'>N-acetyl-d-glucosamine locations!</scene> N-acetyl-D-glucosamine may regulate integrin signaling during cancer cell migration<ref>PMID:19755493</ref>.

[[Image:Integrin.png|200 px|thumb|Fig. 1: Schematic of integrin heterodimers binding to ECM proteins]]

==Integrins and cancer==

Integrins binding to the extracellular matrix provide cells the ability to migrate and remodel the surrounding microenvironment. Integrins are extremely important in cancer metastasis and the progression of solid tumors. Cells bind to extracellular matrix proteins, like<scene name='60/609772/Rgd_bound/2'> peptide RGD (black) on fibronectin</scene>, with integrins to stimulate survival, migration/invasion, and proliferation <ref>PMID:20029421</ref>. Though high expression of integrin beta 1 has been shown to drive primary tumor progression and metastasis, targeting integrins for cancer treatment has seen limited clinical efficacy <ref>PMID:22894137</ref>. These failures stem from differential integrin expression between cancer cells, but new technologies to screen cancer cell populations are being developed to affective therapies on a patient-specific level <ref> Barney LE, Dandley EC, Jansen LE, Reich NG, Mercurio AM, Peyton SR. “A Cell-ECM Screening Method to Predict Breast Cancer Metastasis”. (2014) In Review.</ref>. These technologies will likely allow for more selective treatment and better clinical efficacy for integrin inhibitors.
[[Image:B1_tissue.png|200 px|thumb|Fig. 2: Beta1 integrin expression in a human breast tumor stained in the Peyton Lab. Beta1 integrin (red) is expressed in the tumor cells. DAPI stains the nuclei in blue.]]

==Studying Integrin Beta-1'' in vitro''==

Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins)<ref>PMID:7955174</ref>, and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM<ref>PMID:9105051 </ref>. When beta1 dimerizes with alpha1, it can bind to both collagens I and IV as well as laminins <ref>PMID: 12662928</ref>, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. </scene> These tools are especially useful when microenvironment stiffness<ref>PMID:20939067</ref> or composition<ref>PMID:15183609</ref> are controlled, allowing for examination of the effect of each of these cues on cell phenotype<ref>PMID:8074327</ref> or downstream signaling.

[[Image:231_beta1.png|315 px|thumb|Fig. 3: Beta1 integrin expression in the human breast cancer cell line MDA-MB-231 stained in the Peyton Lab. Beta1 integrin (green) is expressed mainly around the periphery. DAPI stains the nuclei in blue. Scale bar is 50 microns.]]

==Peyton Lab Research Interests==
The [http://www.peytonlab.org/ Peyton lab] studies how cells process chemical and physical cues from the extracellular matrix and how these interactions play a role in the progression of cardiovascular disease and cancer. We aim to understand the downstream signaling pathways activated when cells use their integrins to bind to matrix and how this translates to the disease of interest. We are further interested in how integrins can be biomarkers in disease, because they transduce signals from the diseased microenvironment to cells, likely facilitating disease progression in some cases.

==References==
<references/>

Molecular Playground/IntegrinBeta1

2014-11-20T18:44:29Z

Elizabeth Brooks:

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
Molecular Playground banner: '''"

'''Banner:''' Studying integrin-mediated metastasis ''in vitro''

<Structure load='3VI4' size='350' frame='true' align='right' caption='Integrin Beta 1 Alpha 5' scene='60/609772/Integrinb1alpha5/1' />
==Structure==
Integrins are surface proteins that are comprised of an alpha subunit and a beta subunit to form a functional transmembrane structure. The subunits of the heterodimer each have small cytoplasmic domains for signal transduction within the cell.
Blue-Alpha 5 chain
Red-Beta 1 chain
Grey-SG/19 Fab fragment light chain
Green-SG/19 Fab fragment heavy chain

==Function==

Integrins are a class of surface proteins that bind to extracellular matrix components and transmit chemical and mechanical cues to internal signaling pathways. Integrin beta 1 binds many proteins when dimerized with an alpha subunit, including <scene name='60/609772/Integrinbeta1_binding_collagen/1'>collagen</scene>, laminin and fibronectin. Integrin adhesion to the extra cellular matrix is key for cell ability to adhere, migrate and proliferate in both 2D and 3D systems. These will eventually form adhesion complexes, which regulate actomyocin polymerization. During migration, cells continually form new focal adhesions at the leading edge of the cell and release adhesion complexes at the back of the cell, enabling forward movement.

Here are the <scene name='60/609772/N-acetyl-d-glucosamine/2'>N-acetyl-d-glucosamine locations!</scene> N-acetyl-D-glucosamine may regulate integrin signaling during cancer cell migration<ref>PMID:19755493</ref>.

==Integrins and cancer==

Integrins binding to the extracellular matrix provide cells the ability to migrate and remodel the surrounding microenvironment. Integrins are extremely important in cancer metastasis and the progression of solid tumors. Cells bind to extracellular matrix proteins, like<scene name='60/609772/Rgd_bound/2'> peptide RGD (black) on fibronectin</scene>, with integrins to stimulate survival, migration/invasion, and proliferation <ref>PMID:20029421</ref>. Though high expression of integrin beta 1 has been shown to drive primary tumor progression and metastasis, targeting integrins for cancer treatment has seen limited clinical efficacy <ref>PMID:22894137</ref>. These failures stem from differential integrin expression between cancer cells, but new technologies to screen cancer cell populations are being developed to affective therapies on a patient-specific level <ref> Barney LE, Dandley EC, Jansen LE, Reich NG, Mercurio AM, Peyton SR. “A Cell-ECM Screening Method to Predict Breast Cancer Metastasis”. (2014) In Review.</ref>. These technologies will likely allow for more selective treatment and better clinical efficacy for integrin inhibitors.

==Studying Integrin Beta-1'' in vitro''==

Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins)<ref>PMID:7955174</ref>, and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM<ref>PMID:9105051 </ref>. When beta1 dimerizes with alpha1, it can bind to both collagens I and IV as well as laminins <ref>PMID: 12662928</ref>, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. </scene> These tools are especially useful when microenvironment stiffness<ref>PMID:20939067</ref> or composition<ref>PMID:15183609</ref> are controlled, allowing for examination of the effect of each of these cues on cell phenotype<ref>PMID:8074327</ref> or downstream signaling.

==Peyton Lab Research Interests==
The [http://www.peytonlab.org/ Peyton lab] studies how cells process chemical and physical cues from the extracellular matrix and how these interactions play a role in the progression of cardiovascular disease and cancer. We aim to understand the downstream signaling pathways activated when cells use their integrins to bind to matrix and how this translates to the disease of interest. We are further interested in how integrins can be biomarkers in disease, because they transduce signals from the diseased microenvironment to cells, likely facilitating disease progression in some cases.
</StructureSection>
==References==
<references/>

Elizabeth Brooks/Sandbox1

2014-11-20T18:24:08Z

Elizabeth Brooks:

==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Elizabeth Brooks/Sandbox1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==
<scene name='60/609772/Integrinbeta1_binding_collagen/1'>Integrin Beta 1 binding to collagen</scene>
== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Elizabeth Brooks/Sandbox1

2014-11-20T18:23:18Z

Elizabeth Brooks:

==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Elizabeth Brooks/Sandbox1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==
<scene name='60/609772/Integrinbeta1_binding_collagen/1'>TextToBeDisplayed</scene>
== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Molecular Playground/IntegrinBeta1

2014-11-20T18:20:18Z

Elizabeth Brooks:

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
Molecular Playground banner: '''"

'''Banner:''' Studying integrin-mediated metastasis ''in vitro''

<Structure load='3VI4' size='350' frame='true' align='right' caption='Integrin Beta 1 Alpha 5' scene='60/609772/Integrinb1alpha5/1' />
==Structure==
Integrins are comprised of one alpha and one beta transmembrane subunits.
Blue-Alpha 5 chain
Red-Beta 1 chain
Grey-SG/19 Fab fragment light chain
Green-SG/19 Fab fragment heavy chain

==Function==

Integrins are a class of surface proteins that bind to extracellular matrix components and transmit chemical and mechanical cues to internal signaling pathways. Integrin beta 1 binds many proteins when dimerized with an alpha subunit, including <scene name='60/609772/Integrinbeta1_binding_collagen/1'>collagen</scene>, laminin and fibronectin. Integrin adhesion to the extra cellular matrix is key for cell ability to adhere, migrate and proliferate in both 2D and 3D systems. These will eventually form adhesion complexes, which regulate actomyocin polymerization. During migration, cells continually form new focal adhesions at the leading edge of the cell and release adhesion complexes at the back of the cell, enabling forward movement.

Here are the <scene name='60/609772/N-acetyl-d-glucosamine/2'>N-acetyl-d-glucosamine locations!</scene> N-acetyl-D-glucosamine may regulate integrin signaling during cancer cell migration<ref>PMID:19755493</ref>.

==Integrins and cancer==

Integrins binding to the extracellular matrix provide cells the ability to migrate and remodel the surrounding microenvironment. Integrins are extremely important in cancer metastasis and the progression of solid tumors. Cells bind to extracellular matrix proteins, like<scene name='60/609772/Rgd_bound/2'> peptide RGD (black) on fibronectin</scene>, with integrins to stimulate survival, migration/invasion, and proliferation <ref>PMID:20029421</ref>. Though high expression of integrin beta 1 has been shown to drive primary tumor progression and metastasis, targeting integrins for cancer treatment has seen limited clinical efficacy <ref>PMID:22894137</ref>. These failures stem from differential integrin expression between cancer cells, but new technologies to screen cancer cell populations are being developed to affective therapies on a patient-specific level <ref> Barney LE, Dandley EC, Jansen LE, Reich NG, Mercurio AM, Peyton SR. “A Cell-ECM Screening Method to Predict Breast Cancer Metastasis”. (2014) In Review.</ref>. These technologies will likely allow for more selective treatment and better clinical efficacy for integrin inhibitors.

==Studying Integrin Beta-1'' in vitro''==

Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins)<ref>PMID:7955174</ref>, and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM<ref>PMID:9105051 </ref>. When beta1 dimerizes with alpha1, it can bind to both collagens I and IV as well as laminins <ref>PMID: 12662928</ref>, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. </scene> These tools are especially useful when microenvironment stiffness<ref>PMID:20939067</ref> or composition<ref>PMID:15183609</ref> are controlled, allowing for examination of the effect of each of these cues on cell phenotype<ref>PMID:8074327</ref> or downstream signaling.

==Peyton Lab Research Interests==
The [http://www.peytonlab.org/ Peyton lab] studies how cells process chemical and physical cues from the extracellular matrix and how these interactions play a role in the progression of cardiovascular disease and cancer. We aim to understand the downstream signaling pathways activated when cells use their integrins to bind to matrix and how this translates to the disease of interest. We are further interested in how integrins can be biomarkers in disease, because they transduce signals from the diseased microenvironment to cells, likely facilitating disease progression in some cases.
</StructureSection>
==References==
<references/>

Molecular Playground/IntegrinBeta1

2014-11-20T18:07:10Z

Elizabeth Brooks:

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
Molecular Playground banner: '''"

'''Banner:''' Studying integrin-mediated metastasis ''in vitro''

<Structure load='3VI4' size='350' frame='true' align='right' caption='Integrin Beta 1 Alpha 5' scene='60/609772/Integrinb1alpha5/1' />
==Structure==
Integrins are comprised of one alpha and one beta transmembrane subunits.
Blue-Alpha 5 chain
Red-Beta 1 chain
Grey-SG/19 Fab fragment light chain
Green-SG/19 Fab fragment heavy chain

==Function==

Integrins are a class of surface proteins that bind to extracellular matrix components and transmit chemical and mechanical cues to internal signaling pathways. Integrin beta 1 binds many proteins when dimerized with an alpha subunit, including collagen, laminin and fibronectin. Integrin adhesion to the extra cellular matrix is key for cell ability to adhere, migrate and proliferate in both 2D and 3D systems. These will eventually form adhesion complexes, which regulate actomyocin polymerization. During migration, cells continually form new focal adhesions at the leading edge of the cell and release adhesion complexes at the back of the cell, enabling forward movement.

Here are the <scene name='60/609772/N-acetyl-d-glucosamine/2'>N-acetyl-d-glucosamine locations!</scene> N-acetyl-D-glucosamine may regulate integrin signaling during cancer cell migration<ref>PMID:19755493</ref>.

==Integrins and cancer==

Integrins binding to the extracellular matrix provide cells the ability to migrate and remodel the surrounding microenvironment. Integrins are extremely important in cancer metastasis and the progression of solid tumors. Cells bind to extracellular matrix proteins, like<scene name='60/609772/Rgd_bound/2'> peptide RGD (black) on fibronectin</scene>, with integrins to stimulate survival, migration/invasion, and proliferation <ref>PMID:20029421</ref>. Though high expression of integrin beta 1 has been shown to drive primary tumor progression and metastasis, targeting integrins for cancer treatment has seen limited clinical efficacy <ref>PMID:22894137</ref>. These failures stem from differential integrin expression between cancer cells, but new technologies to screen cancer cell populations are being developed to affective therapies on a patient-specific level <ref> Barney LE, Dandley EC, Jansen LE, Reich NG, Mercurio AM, Peyton SR. “A Cell-ECM Screening Method to Predict Breast Cancer Metastasis”. (2014) In Review.</ref>. These technologies will likely allow for more selective treatment and better clinical efficacy for integrin inhibitors.

==Studying Integrin Beta-1'' in vitro''==

Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins)<ref>PMID:7955174</ref>, and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM<ref>PMID:9105051 </ref>. When beta1 dimerizes with alpha1, it can bind to both collagens I and IV as well as laminins <ref>PMID: 12662928</ref>, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. </scene> These tools are especially useful when microenvironment stiffness<ref>PMID:20939067</ref> or composition<ref>PMID:15183609</ref> are controlled, allowing for examination of the effect of each of these cues on cell phenotype<ref>PMID:8074327</ref> or downstream signaling.

==Peyton Lab Research Interests==
The [http://www.peytonlab.org/ Peyton lab] studies how cells process chemical and physical cues from the extracellular matrix and how these interactions play a role in the progression of cardiovascular disease and cancer. We aim to understand the downstream signaling pathways activated when cells use their integrins to bind to matrix and how this translates to the disease of interest. We are further interested in how integrins can be biomarkers in disease, because they transduce signals from the diseased microenvironment to cells, likely facilitating disease progression in some cases.
</StructureSection>
==References==
<references/>

Molecular Playground/IntegrinBeta1

2014-11-20T18:04:47Z

Elizabeth Brooks:

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].
Molecular Playground banner: '''"

'''Banner:''' Studying integrin-mediated metastasis ''in vitro''

<Structure load='3VI4' size='350' frame='true' align='right' caption='Integrin Beta 1 Alpha 5' scene='60/609772/Integrinb1alpha5/1' />
==Structure==
Integrins are comprised of one alpha and one beta subunits.
Blue-Alpha 5 chain
Red-Beta 1 chain
Grey-SG/19 Fab fragment light chain
Green-SG/19 Fab fragment heavy chain

==Function==

Integrins are a class of surface proteins that bind to extracellular matrix components and transmit chemical and mechanical cues to internal signaling pathways. Integrin beta 1 binds many proteins when dimerized with an alpha subunit, including collagen, laminin and fibronectin. Integrin adhesion to the extra cellular matrix is key for cell ability to adhere, migrate and proliferate in both 2D and 3D systems. These will eventually form adhesion complexes, which regulate actomyocin polymerization. During migration, cells continually form new focal adhesions at the leading edge of the cell and release adhesion complexes at the back of the cell, enabling forward movement.

Here are the <scene name='60/609772/N-acetyl-d-glucosamine/2'>N-acetyl-d-glucosamine locations!</scene> N-acetyl-D-glucosamine may regulate integrin signaling during cancer cell migration<ref>PMID:19755493</ref>.

==Integrins and cancer==

Integrins binding to the extracellular matrix provide cells the ability to migrate and remodel the surrounding microenvironment. Integrins are extremely important in cancer metastasis and the progression of solid tumors. Cells bind to extracellular matrix proteins, like<scene name='60/609772/Rgd_bound/2'> peptide RGD (black) on fibronectin</scene>, with integrins to stimulate survival, migration/invasion, and proliferation <ref>PMID:20029421</ref>. Though high expression of integrin beta 1 has been shown to drive primary tumor progression and metastasis, targeting integrins for cancer treatment has seen limited clinical efficacy <ref>PMID:22894137</ref>. These failures stem from differential integrin expression between cancer cells, but new technologies to screen cancer cell populations are being developed to affective therapies on a patient-specific level <ref> Barney LE, Dandley EC, Jansen LE, Reich NG, Mercurio AM, Peyton SR. “A Cell-ECM Screening Method to Predict Breast Cancer Metastasis”. (2014) In Review.</ref>. These technologies will likely allow for more selective treatment and better clinical efficacy for integrin inhibitors.

==Studying Integrin Beta-1'' in vitro''==

Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins)<ref>PMID:7955174</ref>, and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM<ref>PMID:9105051 </ref>. When beta1 dimerizes with alpha1, it can bind to both collagens I and IV as well as laminins <ref>PMID: 12662928</ref>, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. </scene> These tools are especially useful when microenvironment stiffness<ref>PMID:20939067</ref> or composition<ref>PMID:15183609</ref> are controlled, allowing for examination of the effect of each of these cues on cell phenotype<ref>PMID:8074327</ref> or downstream signaling.

==Peyton Lab Research Interests==
The [http://www.peytonlab.org/ Peyton lab] studies how cells process chemical and physical cues from the extracellular matrix and how these interactions play a role in the progression of cardiovascular disease and cancer. We aim to understand the downstream signaling pathways activated when cells use their integrins to bind to matrix and how this translates to the disease of interest. We are further interested in how integrins can be biomarkers in disease, because they transduce signals from the diseased microenvironment to cells, likely facilitating disease progression in some cases.
</StructureSection>
==References==
<references/>

Elizabeth Brooks/Sandbox1

2014-11-19T17:27:17Z

Elizabeth Brooks: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...

==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Elizabeth Brooks/Sandbox1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>