Enhanced affinities and specificities of consolidated ligands for the Src homology (SH) 3 and SH2 domains of Abelson protein-tyrosine kinase

David Cowburn, J. Zheng, Q. Xu, G. Barany

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The possible interrelationships between multiple domains of proteins involved in intracellular signal transduction are complex and not easily investigated. We have synthesized a series of bivalent consolidated ligands, which interact simultaneously with the SH2 and SH3 domain of Abelson kinase in a SH(32) dual domain construct, a portion of native Abelson kinase. Affinities were measured by quenching of intrinsic tryptophan fluorescence. Consolidated ligands have enhanced affinity and specificity compared to monovalent equivalents. Affinity is also dependent on the length of the linker joining the two parts, with an optimum distance similar to that expected from structural models of Abl (SH(32). These results suggest that consolidated ligands may be generally useful reagents for probing structural and functional activities of multidomain proteins.

Original languageEnglish (US)
Pages (from-to)26738-26741
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number45
DOIs
StatePublished - 1995
Externally publishedYes

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src Homology Domains
Protein-Tyrosine Kinases
Ligands
Phosphotransferases
Signal transduction
Structural Models
Tryptophan
Joining
Quenching
Signal Transduction
Proteins
Fluorescence

ASJC Scopus subject areas

  • Biochemistry

Cite this

Enhanced affinities and specificities of consolidated ligands for the Src homology (SH) 3 and SH2 domains of Abelson protein-tyrosine kinase. / Cowburn, David; Zheng, J.; Xu, Q.; Barany, G.

In: Journal of Biological Chemistry, Vol. 270, No. 45, 1995, p. 26738-26741.

Research output: Contribution to journalArticle

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