Altered cell adhesion and cell viability in a p38 alpha mitogen-activated protein kinase-deficient mouse embryonic stem cell line

Yan-Lin Guo, University of Southern Mississippi
Baohua Yang

Abstract

p38 mitogen-activated protein (MAP) kinase alpha (p38 alpha) is a broadly expressed protein kinase that regulates growth and development. Most studies of p38 alpha have been in somatic cells. Little is known about its function in embryonic stem (ES) cells. Using a ES cell line isolated from p38 alpha knockout mouse embryos (p38 alpha(-/-) ES cells), we investigated roles of p38 alpha in the regulation of ES cell activities. p38 alpha(-/-) ES cells displayed several altered features different from wild-type cells. The major findings are that p38 alpha(-/-) ES cells have significantly increased cell adhesion to several extracelluar matrix proteins, correlating with elevated phosphorylation of focal adhesion kinase and paxillin. p38 alpha(-/-) 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. p38 alpha(-/-) 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 p38 alpha(-/-) ES cells, but rather is likely a result of improved cell adhesion and/or cell viability. Together our results indicated that p38 alpha may negatively regulate mouse ES cell adhesion and viability.