| RACK1: a novel substrate for the Src protein-tyrosine kinase. | |
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MedLine Citation:
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PMID: 12400005 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RACK1 is one of a group of PKC-interacting proteins collectively called RACKs (Receptors for Activated C-Kinases). Previously, we showed that RACK1 also interacts with the Src tyrosine kinase, and is an inhibitor of Src activity and cell growth. PKC activation induces the intracellular movement and co-localization of RACK1 and Src, and the tyrosine phosphorylation of RACK1. To determine whether RACK1 is a Src substrate, we assessed phosphorylation of RACK1 by various tyrosine kinases in vitro, and by kinase-active and inactive mutants of Src in vivo. We found that RACK1 is a Src substrate. Moreover, Src activity is necessary for both the tyrosine phosphorylation of RACK1 and the binding of RACK1 to Src's SH2 domain that occur following PKC activation. To identify the tyrosine(s) on RACK1 that is phosphorylated by Src, we generated and tested a series of RACK1 mutants. We found that Src phosphorylates RACK1 on Tyr 228 and/or Tyr 246, highly-conserved tyrosines located in the sixth WD repeat that interact with Src's SH2 domain. We think that RACK1 is an important Src substrate that signals downstream of growth factor receptor tyrosine kinases and is involved in the regulation of Src function and cell growth. |
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Authors:
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Betty Y Chang; Rachel A Harte; Christine A Cartwright |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Oncogene Volume: 21 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2002 Oct |
Date Detail:
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Created Date: 2002-10-25 Completed Date: 2002-11-19 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 7619-29 Citation Subset: IM |
Affiliation:
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Department of Medicine, Stanford University, Stanford, California, CA 94305, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Amino Acid Sequence Amino Acid Substitution Animals Binding Sites CHO Cells Cricetinae Mice Molecular Sequence Data Oncogene Proteins v-abl / metabolism Phosphorylation Protein Kinase C / metabolism Receptor, Epidermal Growth Factor / metabolism Receptors, Cell Surface / genetics, metabolism* Receptors, Platelet-Derived Growth Factor / metabolism Repetitive Sequences, Amino Acid Sequence Homology, Amino Acid Substrate Specificity Tyrosine / metabolism src Homology Domains src-Family Kinases / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA69810/CA/NCI NIH HHS; R01 DK43743/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Oncogene Proteins v-abl; 0/Receptors, Cell Surface; 0/receptors for activated C kinase; 55520-40-6/Tyrosine; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor; EC 2.7.10.2/src-Family Kinases; EC 2.7.11.13/Protein Kinase C |
| Comments/Corrections | |
Erratum In:
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Oncogene. 2003 Mar 20;22(11):1748 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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