PMID: 9647655Jul 1, 1998Paper

Src family tyrosine kinase regulates intracellular pH in cardiomyocytes

The Journal of Cell Biology
M PucéatG Vassort

Abstract

The Anion Cl-/HCO3- Exchangers AE1, AE2, and AE3 are membrane pH regulatory ion transporters ubiquitously expressed in vertebrate tissues. Besides relieving intracellular alkaline and CO2 loads, the AEs have an important function during development and cell death and play a central role in such cellular properties as cell shape, metabolism, and contractility. The activity of AE(s) are regulated by neurohormones. However, little is known as to the intracellular signal transduction pathways that underlie this modulation. We show here that, in cardiomyocytes that express both AE1 and AE3, the purinergic agonist, ATP, triggers activation of anion exchange. The AE activation is observed in cells in which AE3 expression was blocked but not in cells microinjected with neutralizing anti-AE1 antibodies. ATP induces tyrosine phosphorylation of AE1, activation of the tyrosine kinase Fyn, and association of both Fyn and FAK with AE1. Inhibition of Src family kinases in vivo by genistein, herbimycin A, or ST638 prevents purinergic activation of AE1. Microinjection of either anti-Cst.1 antibody or recombinant CSK, both of which prevent activation of Src family kinase, significantly decreases ATP-induced activation of AE. Microinjection of an...Continue Reading

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Citations

May 22, 2013·Purinergic Signalling·Juan Pablo ReyesS Jeffrey Dixon
May 1, 2001·DNA Sequence : the Journal of DNA Sequencing and Mapping·B E ShmuklerS L Alper
Jan 19, 2016·Journal of Theoretical Biology·Ekaterina S ChernyshovaAndrei V Chernyshev
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