αB-crystallin interacts with and prevents stress-activated proteolysis of focal adhesion kinase by calpain in cardiomyocytes
Focal adhesion kinase (FAK) contributes to cellular homeostasis under stress conditions. Here we show that αB-crystallin interacts with and confers protection to FAK against calpain-mediated proteolysis in cardiomyocytes. A hydrophobic patch mapped between helices 1 and 4 of the FAK FAT domain was f...
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| Veröffentlicht in: | Nature communications 2014-10, Vol.5 (1), p.5159-5159, Article 5159 |
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| creator | Pereira, Michelle B. M. Santos, Aline M. Gonçalves, Danieli C. Cardoso, Alisson C. Consonni, Sílvio R. Gozzo, Fabio C. Oliveira, Paulo S. Pereira, Ana Helena M. Figueiredo, Alana R. Tiroli-Cepeda, Ana O. Ramos, Carlos H. I. de Thomaz, André A. Cesar, Carlos L. Franchini, Kleber G. |
| description | Focal adhesion kinase (FAK) contributes to cellular homeostasis under stress conditions. Here we show that αB-crystallin interacts with and confers protection to FAK against calpain-mediated proteolysis in cardiomyocytes. A hydrophobic patch mapped between helices 1 and 4 of the FAK FAT domain was found to bind to the β4–β8 groove of αB-crystallin. Such an interaction requires FAK tyrosine 925 and is enhanced following its phosphorylation by Src, which occurs upon FAK stimulation. αB-crystallin silencing results in calpain-dependent FAK depletion and in the increased apoptosis of cardiomyocytes in response to mechanical stress. FAK overexpression protects cardiomyocytes depleted of αB-crystallin against the stretch-induced apoptosis. Consistently, load-induced apoptosis is blunted in the hearts from cardiac-specific FAK transgenic mice transiently depleted of αB-crystallin by RNA interference. These studies define a role for αB-crystallin in controlling FAK function and cardiomyocyte survival through the prevention of calpain-mediated degradation of FAK.
Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein, critical for proper cardiac function under stress conditions. Here the authors show that the small heat–shock protein αB-crystallin interacts with FAK and protects it from calpain-mediated proteolysis in stressed rat cardiomyocytes. |
| doi_str_mv | 10.1038/ncomms6159 |
| format | Article |
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Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein, critical for proper cardiac function under stress conditions. Here the authors show that the small heat–shock protein αB-crystallin interacts with FAK and protects it from calpain-mediated proteolysis in stressed rat cardiomyocytes.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/ncomms6159</identifier><identifier>PMID: 25319025</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/58 ; 13 ; 14 ; 14/19 ; 42/70 ; 42/89 ; 631/80/474 ; 631/80/86/2366 ; 692/699/75 ; 82 ; 96 ; 96/2 ; alpha-Crystallin B Chain - chemistry ; Animals ; Aorta - metabolism ; Apoptosis ; Calpain - metabolism ; Cell Survival ; Fluorescence Resonance Energy Transfer ; Focal Adhesion Protein-Tyrosine Kinases - metabolism ; Gene Expression Regulation, Enzymologic ; Gene Silencing ; Homeostasis ; Humanities and Social Sciences ; Male ; Mice ; Mice, Transgenic ; Microscopy, Fluorescence ; Models, Molecular ; multidisciplinary ; Myocardium - metabolism ; Myocytes, Cardiac - cytology ; Phosphorylation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Rats, Wistar ; Science ; Science (multidisciplinary) ; src-Family Kinases - metabolism ; Stress, Mechanical</subject><ispartof>Nature communications, 2014-10, Vol.5 (1), p.5159-5159, Article 5159</ispartof><rights>Springer Nature Limited 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-c560db1fe69ef6d81d24c66ec60d6bf18a4bea3828014a7cc2975ac9274af30f3</citedby><cites>FETCH-LOGICAL-c359t-c560db1fe69ef6d81d24c66ec60d6bf18a4bea3828014a7cc2975ac9274af30f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncomms6159$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://doi.org/10.1038/ncomms6159$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41096,42165,51551</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/ncomms6159$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25319025$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pereira, Michelle B. M.</creatorcontrib><creatorcontrib>Santos, Aline M.</creatorcontrib><creatorcontrib>Gonçalves, Danieli C.</creatorcontrib><creatorcontrib>Cardoso, Alisson C.</creatorcontrib><creatorcontrib>Consonni, Sílvio R.</creatorcontrib><creatorcontrib>Gozzo, Fabio C.</creatorcontrib><creatorcontrib>Oliveira, Paulo S.</creatorcontrib><creatorcontrib>Pereira, Ana Helena M.</creatorcontrib><creatorcontrib>Figueiredo, Alana R.</creatorcontrib><creatorcontrib>Tiroli-Cepeda, Ana O.</creatorcontrib><creatorcontrib>Ramos, Carlos H. I.</creatorcontrib><creatorcontrib>de Thomaz, André A.</creatorcontrib><creatorcontrib>Cesar, Carlos L.</creatorcontrib><creatorcontrib>Franchini, Kleber G.</creatorcontrib><title>αB-crystallin interacts with and prevents stress-activated proteolysis of focal adhesion kinase by calpain in cardiomyocytes</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Focal adhesion kinase (FAK) contributes to cellular homeostasis under stress conditions. Here we show that αB-crystallin interacts with and confers protection to FAK against calpain-mediated proteolysis in cardiomyocytes. A hydrophobic patch mapped between helices 1 and 4 of the FAK FAT domain was found to bind to the β4–β8 groove of αB-crystallin. Such an interaction requires FAK tyrosine 925 and is enhanced following its phosphorylation by Src, which occurs upon FAK stimulation. αB-crystallin silencing results in calpain-dependent FAK depletion and in the increased apoptosis of cardiomyocytes in response to mechanical stress. FAK overexpression protects cardiomyocytes depleted of αB-crystallin against the stretch-induced apoptosis. Consistently, load-induced apoptosis is blunted in the hearts from cardiac-specific FAK transgenic mice transiently depleted of αB-crystallin by RNA interference. These studies define a role for αB-crystallin in controlling FAK function and cardiomyocyte survival through the prevention of calpain-mediated degradation of FAK.
Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein, critical for proper cardiac function under stress conditions. Here the authors show that the small heat–shock protein αB-crystallin interacts with FAK and protects it from calpain-mediated proteolysis in stressed rat cardiomyocytes.</description><subject>101/58</subject><subject>13</subject><subject>14</subject><subject>14/19</subject><subject>42/70</subject><subject>42/89</subject><subject>631/80/474</subject><subject>631/80/86/2366</subject><subject>692/699/75</subject><subject>82</subject><subject>96</subject><subject>96/2</subject><subject>alpha-Crystallin B Chain - chemistry</subject><subject>Animals</subject><subject>Aorta - metabolism</subject><subject>Apoptosis</subject><subject>Calpain - metabolism</subject><subject>Cell Survival</subject><subject>Fluorescence Resonance Energy Transfer</subject><subject>Focal Adhesion Protein-Tyrosine Kinases - metabolism</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Gene Silencing</subject><subject>Homeostasis</subject><subject>Humanities and Social Sciences</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Fluorescence</subject><subject>Models, Molecular</subject><subject>multidisciplinary</subject><subject>Myocardium - metabolism</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Phosphorylation</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>src-Family Kinases - metabolism</subject><subject>Stress, Mechanical</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkD1OxDAQhS0EAgQ0HAC5RKCAHSfZuATEn4REA3XkOGMwJPbi8S5KwaG4CGfCsPwVTDOj9z492Y-Qbc4OOBP1odN-GLDipVwi6zkreMYnuVj-c6-RLcQHlkZIXhfFKlnLS8Ely8t18vL2epzpMGJUfW8dtS5CUDoifbbxnirX0WmAObikYAyAmCXXzlWED8dH8P2IFqk31Hiteqq6e0DrHX20TiHQdqRJnqrP8HSGzvph9HqMgJtkxageYetrb5Dbs9Obk4vs6vr88uToKtOilDHTZcW6lhuoJJiqq3mXF7qqQCe5ag2vVdGCEnVeM16oida5nJRKy3xSKCOYERtkd5GbXvw0A4zNYFFD3ysHfoYNr7iQpaglS-jeAtXBIwYwzTTYQYWx4az5aLz5bTzBO1-5s3aA7gf97jcB-wsAk-XuIDQPfhZc-ut_ce8a3o_m</recordid><startdate>20141016</startdate><enddate>20141016</enddate><creator>Pereira, Michelle B. 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M. ; Santos, Aline M. ; Gonçalves, Danieli C. ; Cardoso, Alisson C. ; Consonni, Sílvio R. ; Gozzo, Fabio C. ; Oliveira, Paulo S. ; Pereira, Ana Helena M. ; Figueiredo, Alana R. ; Tiroli-Cepeda, Ana O. ; Ramos, Carlos H. 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M.</creatorcontrib><creatorcontrib>Santos, Aline M.</creatorcontrib><creatorcontrib>Gonçalves, Danieli C.</creatorcontrib><creatorcontrib>Cardoso, Alisson C.</creatorcontrib><creatorcontrib>Consonni, Sílvio R.</creatorcontrib><creatorcontrib>Gozzo, Fabio C.</creatorcontrib><creatorcontrib>Oliveira, Paulo S.</creatorcontrib><creatorcontrib>Pereira, Ana Helena M.</creatorcontrib><creatorcontrib>Figueiredo, Alana R.</creatorcontrib><creatorcontrib>Tiroli-Cepeda, Ana O.</creatorcontrib><creatorcontrib>Ramos, Carlos H. I.</creatorcontrib><creatorcontrib>de Thomaz, André A.</creatorcontrib><creatorcontrib>Cesar, Carlos L.</creatorcontrib><creatorcontrib>Franchini, Kleber G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Nature communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Pereira, Michelle B. M.</au><au>Santos, Aline M.</au><au>Gonçalves, Danieli C.</au><au>Cardoso, Alisson C.</au><au>Consonni, Sílvio R.</au><au>Gozzo, Fabio C.</au><au>Oliveira, Paulo S.</au><au>Pereira, Ana Helena M.</au><au>Figueiredo, Alana R.</au><au>Tiroli-Cepeda, Ana O.</au><au>Ramos, Carlos H. I.</au><au>de Thomaz, André A.</au><au>Cesar, Carlos L.</au><au>Franchini, Kleber G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>αB-crystallin interacts with and prevents stress-activated proteolysis of focal adhesion kinase by calpain in cardiomyocytes</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2014-10-16</date><risdate>2014</risdate><volume>5</volume><issue>1</issue><spage>5159</spage><epage>5159</epage><pages>5159-5159</pages><artnum>5159</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Focal adhesion kinase (FAK) contributes to cellular homeostasis under stress conditions. Here we show that αB-crystallin interacts with and confers protection to FAK against calpain-mediated proteolysis in cardiomyocytes. A hydrophobic patch mapped between helices 1 and 4 of the FAK FAT domain was found to bind to the β4–β8 groove of αB-crystallin. Such an interaction requires FAK tyrosine 925 and is enhanced following its phosphorylation by Src, which occurs upon FAK stimulation. αB-crystallin silencing results in calpain-dependent FAK depletion and in the increased apoptosis of cardiomyocytes in response to mechanical stress. FAK overexpression protects cardiomyocytes depleted of αB-crystallin against the stretch-induced apoptosis. Consistently, load-induced apoptosis is blunted in the hearts from cardiac-specific FAK transgenic mice transiently depleted of αB-crystallin by RNA interference. These studies define a role for αB-crystallin in controlling FAK function and cardiomyocyte survival through the prevention of calpain-mediated degradation of FAK.
Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein, critical for proper cardiac function under stress conditions. Here the authors show that the small heat–shock protein αB-crystallin interacts with FAK and protects it from calpain-mediated proteolysis in stressed rat cardiomyocytes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25319025</pmid><doi>10.1038/ncomms6159</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 101/58 13 14 14/19 42/70 42/89 631/80/474 631/80/86/2366 692/699/75 82 96 96/2 alpha-Crystallin B Chain - chemistry Animals Aorta - metabolism Apoptosis Calpain - metabolism Cell Survival Fluorescence Resonance Energy Transfer Focal Adhesion Protein-Tyrosine Kinases - metabolism Gene Expression Regulation, Enzymologic Gene Silencing Homeostasis Humanities and Social Sciences Male Mice Mice, Transgenic Microscopy, Fluorescence Models, Molecular multidisciplinary Myocardium - metabolism Myocytes, Cardiac - cytology Phosphorylation Protein Structure, Secondary Protein Structure, Tertiary Rats Rats, Wistar Science Science (multidisciplinary) src-Family Kinases - metabolism Stress, Mechanical |
| title | αB-crystallin interacts with and prevents stress-activated proteolysis of focal adhesion kinase by calpain in cardiomyocytes |
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