A general strategy for producing conditional alleles of Src-like tyrosine kinases.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

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.

Year of Publication
1995
Journal
Proc Natl Acad Sci U S A
Volume
92
Issue
21
Pages
9805-9
Date Published
1995 Oct 10
ISSN
0027-8424
PubMed ID
7568222
PubMed Central ID
PMC40891
Links
Grant list
CA39612 / CA / NCI NIH HHS / United States
GM-52067 / GM / NIGMS NIH HHS / United States