Open AccessA general strategy for producing conditional alleles of Src-like tyrosine kinases.
Author(s) -
David M. Spencer,
Isabella A. Graef,
David Austin,
Stuart L. Schreiber,
Gerald R. Crabtree
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.21.9805
Subject(s) - proto oncogene tyrosine protein kinase src , sh3 domain , receptor tyrosine kinase , microbiology and biotechnology , tyrosine kinase , tyrosine protein kinase csk , biology , signal transduction , kinase , protein tyrosine phosphatase , sh2 domain , mitogen activated protein kinase , jak stat signaling pathway , biochemistry
The Src-like tyrosine kinases require membrane localization for transformation and probably for their normal role in signal transduction. We utilized this characteristic to prepare Src-like tyrosine kinases that can be readily activated with the rationally designed chemical inducer of dimerization FK1012. Dimerization of cytoplasmic Src-like tyrosine kinases was not sufficient for signaling, but their recruitment to the plasma membrane led to the rapid activation of transcription factors identical to those regulated by crosslinking the antigen receptor. Moreover, recruitment of activated Src-like kinases to the membrane replaced signaling by the T-lymphocyte antigen receptor complex, leading to the activation of both the Ras/protein kinase C and Ca2+/calcineurin pathways normally activated by antigen receptor signaling. Since these chemical inducers of dimerization are cell permeable, this approach permits the production of conditional alleles of any of the Src-like tyrosine kinases, thereby allowing a delineation of their developmental roles.