Premium
Induction of down‐regulation of the kinase activities of Mek, p42 Erk , p90 RSK , and p63 SAMK in chicken embryo fibroblast at the late stage of src ‐induced cellular transformation
Author(s) -
Wang HwaChain R.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199607)168:1<87::aid-jcp11>3.0.co;2-m
Subject(s) - embryo , transformation (genetics) , fibroblast , microbiology and biotechnology , kinase , protein kinase a , biology , cell culture , biochemistry , genetics , gene
Two distinct stages in regulation of protein kinases are detectable upon cellular transformation of CEF induced by pp60 v‐ src . Upon cellular transformation induced by ts v‐ src mutants, the kinase activities of Mek and p42 Erk are rapidly induced at the early stage and significantly decreased at the late stage of cellular transformation. In contrast, a novel p63 SAMK is partially activated at the early stage and is fully activated at the late stage of cellular transformation. However, p90 RSK is activated through the entire course of cellular transformation. In this study, I detect a transient down‐regulation of p90 RSK activity that is inducible in cultures at the late stage of the src ‐induced cellular transformation by an increase of extracellular pH value from 7 to 8 and unidentified components in DMEM, but not in cultures which are at the early stage. Concomitant with down‐regulation of p90 RSK activity, the kinase activities of Mek, p42 Erk , and p63 SAMK are also down‐regulated. Blockage of down‐regulation of p90 RSK activity by pretreatment of cells with different phosphatase inhibitors correlates with blockage of the down‐regulation of either p42 Erk or p63 SAMK activity. Multiple pathways appear to involve in regulation of p90 RSK activity. The discrepancy in regulation of protein kinase activity between the early and late stages of cellular transformation induced by pp60 src may indicate a change in signaling cascades during the progress of cellular transformation. The induction of the down‐regulation event in this study may provide a new approach to investigate the regulation not only of protein kinases but also phosphatases in transformed cells. © 1996 Wiley Liss, Inc.