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Human cervical cancer cells use Ca 2+ signalling, protein tyrosine phosphorylation and MAP kinase in regulatory volume decrease
Author(s) -
Shen MengRu,
Chou ChengYang,
Browning Joseph A.,
Wilkins Robert J.,
Ellory J. Clive
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00347.x
Subject(s) - mitogen activated protein kinase kinase , map kinase kinase kinase , microbiology and biotechnology , ask1 , protein kinase c , protein kinase a , tyrosine kinase , mitogen activated protein kinase , kinase , protein tyrosine phosphatase , map2k7 , chemistry , biology , signal transduction , cyclin dependent kinase 2
1 This study was aimed at identifying the signalling pathways involved in the activation of volume‐regulatory mechanisms of human cervical cancer cells. 2 Osmotic swelling of human cervical cancer cells induced a substantial increase in intracellular Ca 2+ ([Ca 2+ ] i ) by the activation of Ca 2+ entry across the cell membrane, as well as Ca 2+ release from intracellular stores. This Ca 2+ signalling was critical for the normal regulatory volume decrease (RVD) response. 3 The activation of swelling‐activated ion and taurine transport was significantly inhibited by tyrosine kinase inhibitors (genistein and tyrphostin AG 1478) and potentiated by the tyrosine phosphatase inhibitor Na 3 VO 4. However, the Src family of tyrosine kinases was not involved in regulation of the swelling‐activated Cl − channel. 4 Cell swelling triggered mitogen‐activated protein (MAP) kinase cascades leading to the activation of extracellular signal‐regulated kinase 1 and 2 (ERK1/ERK2) and p38 kinase. The volume‐responsive ERK1/ERK2 signalling pathway linked with the activation of K + and Cl − channels, and taurine transport. However, the volume‐regulatory mechanism was independent of the activation of p38 MAP kinase. 5 The phosphorylated ERK1/ERK2 expression following a hypotonic shock was up‐regulated by protein kinase C (PKC) activator phorbol 12‐myristate 13‐acetate (PMA) and down‐regulated by PKC inhibitor staurosporine. The response of ERK activation to hypotonicity also required Ca 2+ entry and depended on tyrosine kinase and mitogen‐activated/ERK‐activating kinase (MEK) activity. 6 Considering the results overall, osmotic swelling promotes the activation of tyrosine kinase and ERK1/ERK2 and raises intracellular Ca 2+ , all of which play a crucial role in the volume‐regulatory mechanism of human cervical cancer cells.