PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation
► PTK6 directly phosphorylates tyrosine residues located on the C-terminal domain of c-Cbl. ► Phosphorylation of c-Cbl by PTK6 promotes degradation of c-Cbl. ► PTK6-induced down-regulation of c-Cbl is mediated by the ubiquitin–proteasome pathway. ► Downstream effects of PTK6-mediated c-Cbl degradati...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2013-02, Vol.431 (4), p.734-739 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Kang, Shin-Ae Lee, Seung-Taek |
| description | ► PTK6 directly phosphorylates tyrosine residues located on the C-terminal domain of c-Cbl. ► Phosphorylation of c-Cbl by PTK6 promotes degradation of c-Cbl. ► PTK6-induced down-regulation of c-Cbl is mediated by the ubiquitin–proteasome pathway. ► Downstream effects of PTK6-mediated c-Cbl degradation include multiple pro-oncogenic conduits.
PTK6 (also known as Brk) is an intracellular tyrosine kinase which induces proliferation, anti-apoptosis, migration, and anchorage-independent growth. Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl. Tyr700, Tyr731, and Tyr774 residues in the C-terminal domain of c-Cbl are major phosphorylation sites targeted by PTK6. The phosphorylated c-Cbl is subjected to auto-ubiquitination and degraded through the ubiquitin–proteasome pathway. These results provide evidence for a novel mechanism demonstrating the oncogenic potential of PTK6 through degradation of c-Cbl, which is an E3 ligase important in down-regulation of oncoproteins. |
| doi_str_mv | 10.1016/j.bbrc.2013.01.046 |
| format | Article |
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PTK6 (also known as Brk) is an intracellular tyrosine kinase which induces proliferation, anti-apoptosis, migration, and anchorage-independent growth. Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl. Tyr700, Tyr731, and Tyr774 residues in the C-terminal domain of c-Cbl are major phosphorylation sites targeted by PTK6. The phosphorylated c-Cbl is subjected to auto-ubiquitination and degraded through the ubiquitin–proteasome pathway. These results provide evidence for a novel mechanism demonstrating the oncogenic potential of PTK6 through degradation of c-Cbl, which is an E3 ligase important in down-regulation of oncoproteins.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2013.01.046</identifier><identifier>PMID: 23352614</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>c-Cbl ; Catalysis ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Down-Regulation ; Gene Knockdown Techniques ; Humans ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Oncoprotein ; Phosphorylation ; Proteasomal degradation ; Proteasome Endopeptidase Complex - metabolism ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Proteolysis ; Proto-Oncogene Proteins c-cbl - metabolism ; PTK6 ; Tyrosine - genetics ; Tyrosine - metabolism ; Ubiquitin</subject><ispartof>Biochemical and biophysical research communications, 2013-02, Vol.431 (4), p.734-739</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-fe29535c9d78667e7cb0308daadb2835d2c5a389b6bbe4d9b34a561877a03bba3</citedby><cites>FETCH-LOGICAL-c356t-fe29535c9d78667e7cb0308daadb2835d2c5a389b6bbe4d9b34a561877a03bba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2013.01.046$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23352614$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Shin-Ae</creatorcontrib><creatorcontrib>Lee, Seung-Taek</creatorcontrib><title>PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>► PTK6 directly phosphorylates tyrosine residues located on the C-terminal domain of c-Cbl. ► Phosphorylation of c-Cbl by PTK6 promotes degradation of c-Cbl. ► PTK6-induced down-regulation of c-Cbl is mediated by the ubiquitin–proteasome pathway. ► Downstream effects of PTK6-mediated c-Cbl degradation include multiple pro-oncogenic conduits.
PTK6 (also known as Brk) is an intracellular tyrosine kinase which induces proliferation, anti-apoptosis, migration, and anchorage-independent growth. Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl. Tyr700, Tyr731, and Tyr774 residues in the C-terminal domain of c-Cbl are major phosphorylation sites targeted by PTK6. The phosphorylated c-Cbl is subjected to auto-ubiquitination and degraded through the ubiquitin–proteasome pathway. These results provide evidence for a novel mechanism demonstrating the oncogenic potential of PTK6 through degradation of c-Cbl, which is an E3 ligase important in down-regulation of oncoproteins.</description><subject>c-Cbl</subject><subject>Catalysis</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Down-Regulation</subject><subject>Gene Knockdown Techniques</subject><subject>Humans</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Oncoprotein</subject><subject>Phosphorylation</subject><subject>Proteasomal degradation</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proteolysis</subject><subject>Proto-Oncogene Proteins c-cbl - metabolism</subject><subject>PTK6</subject><subject>Tyrosine - genetics</subject><subject>Tyrosine - metabolism</subject><subject>Ubiquitin</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD1PwzAQhi0EglL4AwwoI0vCnZ04icSCKqCISjAUic3yV9tUaV3sBKn_HpcWRobTLc_76u4h5AohQ0B-u8yU8jqjgCwDzCDnR2SAUENKEfJjMgAAntIaP87IeQhLAMSc16fkjDJWUI75gIzfpi882Xi3cp0NibFzL43sGrdO3CzR6Ui1Sbfwrp8vkh2arqxpZGdNslm4EMdv2x_8gpzMZBvs5WEPyfvjw3Q0TievT8-j-0mqWcG7dGZpXbBC16asOC9tqRUwqIyURtGKFYbqQrKqVlwpm5tasVwWHKuylMCUkmxIbva98ebP3oZOrJqgbdvKtXV9EMgwZ4xhVUSU7lHtXQjezsTGNyvptwJB7AyKpdgZFDuDAlBEgzF0fejvVfz1L_KrLAJ3e8DGL78a60XQjV3r6MVb3Qnjmv_6vwESi4FE</recordid><startdate>20130222</startdate><enddate>20130222</enddate><creator>Kang, Shin-Ae</creator><creator>Lee, Seung-Taek</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130222</creationdate><title>PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation</title><author>Kang, Shin-Ae ; Lee, Seung-Taek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-fe29535c9d78667e7cb0308daadb2835d2c5a389b6bbe4d9b34a561877a03bba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>c-Cbl</topic><topic>Catalysis</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Down-Regulation</topic><topic>Gene Knockdown Techniques</topic><topic>Humans</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Oncoprotein</topic><topic>Phosphorylation</topic><topic>Proteasomal degradation</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proteolysis</topic><topic>Proto-Oncogene Proteins c-cbl - metabolism</topic><topic>PTK6</topic><topic>Tyrosine - genetics</topic><topic>Tyrosine - metabolism</topic><topic>Ubiquitin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Shin-Ae</creatorcontrib><creatorcontrib>Lee, Seung-Taek</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>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Shin-Ae</au><au>Lee, Seung-Taek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2013-02-22</date><risdate>2013</risdate><volume>431</volume><issue>4</issue><spage>734</spage><epage>739</epage><pages>734-739</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>► PTK6 directly phosphorylates tyrosine residues located on the C-terminal domain of c-Cbl. ► Phosphorylation of c-Cbl by PTK6 promotes degradation of c-Cbl. ► PTK6-induced down-regulation of c-Cbl is mediated by the ubiquitin–proteasome pathway. ► Downstream effects of PTK6-mediated c-Cbl degradation include multiple pro-oncogenic conduits.
PTK6 (also known as Brk) is an intracellular tyrosine kinase which induces proliferation, anti-apoptosis, migration, and anchorage-independent growth. Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl. Tyr700, Tyr731, and Tyr774 residues in the C-terminal domain of c-Cbl are major phosphorylation sites targeted by PTK6. The phosphorylated c-Cbl is subjected to auto-ubiquitination and degraded through the ubiquitin–proteasome pathway. These results provide evidence for a novel mechanism demonstrating the oncogenic potential of PTK6 through degradation of c-Cbl, which is an E3 ligase important in down-regulation of oncoproteins.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23352614</pmid><doi>10.1016/j.bbrc.2013.01.046</doi><tpages>6</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2013-02, Vol.431 (4), p.734-739 |
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| subjects | c-Cbl Catalysis Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Down-Regulation Gene Knockdown Techniques Humans Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Oncoprotein Phosphorylation Proteasomal degradation Proteasome Endopeptidase Complex - metabolism Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Proteolysis Proto-Oncogene Proteins c-cbl - metabolism PTK6 Tyrosine - genetics Tyrosine - metabolism Ubiquitin |
| title | PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation |
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