Ca2+ promotes erythrocyte band 3 tyrosine phosphorylation via dissociation of phosphotyrosine phosphatase from band 3

Yehudit Zipser, Adi Piade, Alexander Barbul, Rafi Korenstein, Nechama S. Kosower*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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The anion-exchange band 3 protein is the main erythrocyte protein that is phosphorylated by protein tyrosine kinase (PTK). We have previously identified a band 3-associated phosphotyrosine phosphatase (PTP) that is normally highly active and prevents the accumulation of band 3 phosphotyrosine. Band 3 tyrosine phosphorylation can be induced by inhibition of PTP (vanadate, thiol oxidation), activation of PTK (hypertonic NaCl) or intracellular increased Ca2+ (mechanism unknown). We now show that there is inhibition of dephosphorylation of band 3 in Ca2+/ionophore-treated erythrocytes and in membranes isolated from the treated cells. These membranes exhibit phosphatase activity upon the addition of exogenous substrate. Dephosphorylation of the endogenous substrate (band 3) can be activated in these membranes by the addition of Mg2+. Thus the inability of PTP to dephosphorylate the band 3 phosphotyrosine is not due to inhibition of the enzyme itself. Ca2+ rise in the erythrocyte causes dissociation of PTP from band 3, thus leaving the kinase unopposed. This is shown by a significant diminution in band 3/PTP co-precipitation. Addition of Mg2+ to these membranes leads to reassociation of band 3 with PTP. The Ca2+-induced inhibition of band 3 dephosphorylation may be due to Ca2+-dependent alterations in membrane components and structure, affecting the interaction of band 3 with PTP. The Ca2+-induced tyrosine phosphorylation, involving an apparent PTP inhibition via dissociation from the substrate, may play a role in signal transduction pathways and in certain pathological disorders associated with increased cell Ca2+.

Original languageEnglish
Pages (from-to)137-144
Number of pages8
JournalBiochemical Journal
Issue number1
StatePublished - 15 Nov 2002


  • Hypertonic
  • Mg
  • Phosphotyrosine phosphatase 1B (PTP1B)
  • Protein tyrosine kinase (PTK)
  • Red blood cell


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