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Altered cell adhesion and cell viability in a p38alpha mitogen-activated protein kinase-deficient mouse embryonic
1Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Abstract:
p38 mitogen-activated protein (MAP) kinase alpha (p38alpha) is a broadly expressed protein kinase that regulates growth and development. Most studies of p38alpha have been in somatic cells. Little is known about its function in embryonic stem (ES) cells. Using a ES cell line isolated from p38alpha knockout mouse embryos (p38alpha (-/-) ES cells), we investigated roles of p38alpha in the regulation of ES cell activities. p38alpha (-/-) ES cells displayed several altered features different from wild-type cells. The major findings are that p38alpha (-/-) ES cells have significantly increased cell adhesion to several extracelluar matrix proteins, correlating with elevated phosphorylation of focal adhesion kinase and paxillin. p38alpha (-/-) 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. p38alpha (-/-) 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 p38alpha (-/-) ES cells, but rather is likely a result of improved cell adhesion and/or cell viability. Together our results indicated that p38alpha may negatively regulate mouse ES cell adhesion and viability.
Insights
p38alpha knockout mouse embryonic stem cells show increased adhesion and viability. This suggests p38alpha negatively regulates these key stem cell functions.
Area of Science:
- Cell Biology
- Molecular Biology
- Stem Cell Research
Background:
- p38 mitogen-activated protein (MAP) kinase alpha (p38alpha) is crucial for growth and development in somatic cells.
- Its role in embryonic stem (ES) cells remains largely uncharacterized.
- Understanding p38alpha's function in ES cells is vital for developmental biology and regenerative medicine.
Purpose of the Study:
- To investigate the function of p38alpha in mouse embryonic stem (ES) cell regulation.
- To determine how the absence of p38alpha affects ES cell adhesion, viability, and proliferation.
Main Methods:
- Utilized a p38alpha knockout mouse embryonic stem cell line (p38alpha (-/-) ES cells).
- Compared p38alpha (-/-) ES cells with wild-type ES cells.
- Assessed cell adhesion to extracellular matrix proteins, cell viability markers, and proliferation rates.
Main Results:
- p38alpha (-/-) ES cells exhibited significantly increased adhesion to extracellular matrix proteins.
- Elevated phosphorylation of focal adhesion kinase and paxillin was observed in p38alpha (-/-) ES cells.
- p38alpha (-/-) ES cells displayed enhanced cell viability, linked to increased survivin expression and AKT activation.
- Faster confluence in p38alpha (-/-) ES cells was attributed to improved adhesion and viability, not proliferation.
Conclusions:
- p38alpha appears to negatively regulate cell adhesion in mouse ES cells.
- p38alpha may also negatively regulate cell viability in mouse ES cells.
- These findings provide new insights into the molecular mechanisms governing ES cell behavior and self-renewal.

