Focal adhesion kinases and calcium/calmodulin-dependent protein kinases regulate protein tyrosine phosphorylation in stallion sperm.
Abstract: Protein tyrosine phosphorylation (PY) is a hallmark of sperm capacitation. In stallion sperm, calcium inhibits PY at pH 7.8). These results show for the first time a role for calcium/calmodulin-dependent kinases in PRKA-dependent sperm PY; a non-PRKA-dependent pathway regulating sperm PY; and the apparent involvement of the FAK family of protein tyrosine kinases downstream in both pathways.
Publication Date: 2013-06-06 PubMed ID: 23595906DOI: 10.1095/biolreprod.112.107078Google Scholar: Lookup
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- Journal Article
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- Non-U.S. Gov't
Summary
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This research studied how protein tyrosine phosphorylation (PY) in stallion sperm is regulated by focal adhesion kinases and calcium/calmodulin-dependent protein kinases. The researchers found that two specific pathways are responsible for PY in stallion sperm, both of which involve the FAK family of protein tyrosine kinases.
Understanding Protein Tyrosine Phosphorylation
- Protein tyrosine phosphorylation (PY) is a critical process in sperm capacitation – the biochemical changes that sperm undergo to gain the ability to fertilize an egg.
- In stallion sperm, PY happens in specific circumstances that involve the presence or absence of calcium and how this is modulated. Calcium at certain levels inhibits PY, unless calmodulin, a calcium-binding messenger protein, is blocked.
The Role of Calcium and Calmodulin
- The researchers used different methods to explore the relationship between calcium, calmodulin, and PY in stallion sperm. They treated the sperm with calcium; calcium and a calmodulin inhibitor; or without added calcium.
- They found that in the absence of added calcium, inhibition of calcium/calmodulin-dependent kinases led to a decrease in PY. PY in this scenario is regulated via a well-known pathway called the canonical PRKA pathway. This did not occur when calmodulin was blocked, suggesting there’s another mechanism for calcium to stimulate PY.
Discovering the Focal Adhesion Kinases (FAKs)
- An inhibitor of Focal Adhesion Kinases (FAKs), a group of calcium-induced protein tyrosine kinases, was used to determine whether they had a role in the process.
- They found that FAKs were involved in regulating PY under both the conditions without added calcium and when calmodulin is blocked. This shows that FAKs are critical for sperm capacitation.
- Two specific members of the FAK family, protein tyrosine kinases 2 and 2B, were found to be specifically active in these situations but not when calcium was present without any calmodulin inhibitors.
Significance of the Study
- This research sheds light on the complex processes leading to the activation of sperm cells for fertilization, specifically the role of PY, and how it is regulated by calcium, calmodulin, and FAKs.
- The discovery of a second pathway regulating PY apart from the known PRKA pathway is significant as it broadens our understanding of sperm capacitation.
- The involvement of FAKs in both these pathways opens new avenues for further research and possible therapeutic interventions.
Cite This Article
APA
González-Fernández L, Macías-García B, Loux SC, Varner DD, Hinrichs K.
(2013).
Focal adhesion kinases and calcium/calmodulin-dependent protein kinases regulate protein tyrosine phosphorylation in stallion sperm.
Biol Reprod, 88(6), 138.
https://doi.org/10.1095/biolreprod.112.107078 Publication
Researcher Affiliations
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas 77843-4466, USA.
MeSH Terms
- Animals
- Calcium / metabolism
- Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
- Calcium-Calmodulin-Dependent Protein Kinases / metabolism
- Enzyme Inhibitors / pharmacology
- Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors
- Focal Adhesion Protein-Tyrosine Kinases / metabolism
- Horses
- Male
- Phosphorylation
- Signal Transduction / drug effects
- Signal Transduction / physiology
- Sperm Capacitation / drug effects
- Sperm Capacitation / physiology
- Sperm Motility / drug effects
- Sperm Motility / physiology
- Spermatozoa / drug effects
- Spermatozoa / metabolism
- Sulfonamides / pharmacology
Citations
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