Altered Cell Adhesion and Cell Viability in a p38 α Mitogen-Activated Protein Kinase-Deficient Mouse Embryonic Stem Cell Line

Abstract

p38 mitogen-activated protein (MAP) kinase α (p38α) is a broadly expressed protein kinase that regulates growth and development. Most studies of p38α have been in somatic cells. Little is known about its function in embryonic stem (ES) cells. Using a ES cell line isolated from p38α knockout mouse embryos (p38α ^–/– ES cells), we investigated roles of p38α in the regulation of ES cell activities. p38α ^–/– ES cells displayed several altered features different from wild-type cells. The major findings are that p38α ^–/– ES cells have significantly increased cell adhesion to several extracelluar matrix proteins, correlating with elevated phosphorylation of focal adhesion kinase and paxillin. p38α ^–/– ES cells also showed increased cell viability, correlating with increased expression of survivin and activation of AKT (protein kinase B), two molecules that are known to improve cell viability. p38α ^–/– ES cells reach confluence faster than wild-type cells in routine cell culture. However, this is not due to a higher cell proliferation rate in p38α ^–/– ES cells, but rather is likely a result of improved cell adhesion and/or cell viability. Together our results indicated that p38α may negatively regulate mouse ES cell adhesion and viability.