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Binding of Bruton's Tyrosine Kinase to Fyn, Lyn, or Hck Through a Src Homology 3 Domain-Mediated Interaction

Cheng, Genhong and Ye, Zheng-Sheng and Baltimore, David (1994) Binding of Bruton's Tyrosine Kinase to Fyn, Lyn, or Hck Through a Src Homology 3 Domain-Mediated Interaction. Proceedings of the National Academy of Sciences of the United States of America, 91 (17). pp. 8152-8155. ISSN 0027-8424. PMCID PMC44563.

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Bruton's tyrosine kinase (Btk) is a recently described B-cell-specific tyrosine kinase. Mutations in this gene lead to human X chromosome-linked agammaglobulinemia and murine X-linked immunodeficiency. Although genetic evidence strongly suggests that Btk plays a crucial role in B-lymphocyte differentiation and activation, its precise mechanism of action remains unknown, primarily because the proteins that it interacts with have not yet been identified. Here, we show that Btk interacts with Src homology 3 domains of Fyn, Lyn, and Hck, protein-tyrosine kinases that get activated upon stimulation of B- and T-cell receptors. These interactions are mediated by two 10-aa motifs in Btk. An analogous site with the same specificity is also present in Itk, the T-cell-specific homologue of Btk. Our data extend the range of interactions mediated by Src homology 3 domains and provide an indication of a link between Btk and established signaling pathways in B lymphocytes.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1994 by National Academy of Sciences Contributed by David Baltimore, April 25, 1994 We thank Dr. Roger Brent for kindly providing us with the yeast two-hybrid system; Dr. Marius Sudol for providing the chicken Fyn cDNA; Drs. Lei Ron, Russ Finley, and Erica Golemis for technical advice; Drs. Ruibao Ren, Patricia Cortes, and Joshy Jacob for suggestions; and Warren Pear, Benjamin Chen, and Kalle Saksela for manuscript assistance. G.C. and Z.-S.Y. are recipients of an Irvington House Institute fellowship and a Leukemia Society special fellowship, respectively. This work was supported by National Institute of Allergy and Infectious Diseases Grant A122346 to D.B. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
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Irvington Institute for Medical ResearchUNSPECIFIED
Leukemia Society of AmericaUNSPECIFIED
Issue or Number:17
PubMed Central ID:PMC44563
Record Number:CaltechAUTHORS:CHEpnas94
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Official Citation:Binding of Bruton's tyrosine kinase to Fyn, Lyn, or Hck through a Src homology 3 domain-mediated interaction G Cheng, Z S Ye, D Baltimore Proceedings of the National Academy of Sciences Aug 1994, 91 (17) 8152-8155; DOI: 10.1073/pnas.91.17.8152
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7045
Deposited By: Archive Administrator
Deposited On:06 Jan 2007
Last Modified:23 Apr 2020 22:57

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