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Participation of annexins in protein phosphorylation
1Equipe de Recherche sur la Biologie Cellulaire et Moléculaire des Médiateurs Lipidiques et des Lipoprotéines, C.N.R.S. URA 1283, CHU Saint Antoine, Paris, France. rothhut@ccr.jussieu.fr
Abstract:
Simultaneous discovery of members of the annexin family of calcium and phospholipid binding proteins by several groups is intimately linked to the possibility that these proteins may be controlled by phosphorylation. Indeed, annexin I and annexin II have been identified as major substrates for the tyrosine kinase activity associated with epidermal growth factor receptor (EGF-R) and for the retrovirus encoded protein tyrosine kinase pp60v-arc. Both annexins are also in vitro and/or in situ substrates for platelet derived growth factor (PDGF), insulin and hepatocyte growth factor/scatter factor (HGF/SF) receptor tyrosine kinases. In addition, to serve as substrates for tyrosine protein kinases some annexins are cellular targets for serine threonine protein kinases such as protein kinase C (PKC) and cAMP-dependent protein kinase A (PKA). Although the role of annexin phosphorylation has not been studied in detail, it is thought to influence their vesicle aggregation and phospholipid binding properties. Some annexins are also potent inhibitors of various serine/threonine and tyrosine kinases. The physiological functions of the annexins have still not been clearly defined. Therefore the identification of the ability of these proteins to undergo phosphorylation may be helpful in assigning them a precise biological role.
Insights
Annexin proteins, crucial for cell signaling, are regulated by phosphorylation. This modification by various kinases influences their function and may help define their biological roles.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Annexins are calcium and phospholipid-binding proteins implicated in various cellular processes.
- The discovery of annexins is linked to their potential regulation by phosphorylation.
- Several receptor tyrosine kinases and serine/threonine kinases target annexins.
Purpose of the Study:
- To explore the role of phosphorylation in annexin protein function.
- To investigate annexins as substrates for various protein kinases.
- To elucidate the biological significance of annexin phosphorylation.
Main Methods:
- Identification of annexins as substrates for epidermal growth factor receptor (EGF-R) and pp60v-src tyrosine kinases.
- Demonstration of annexin phosphorylation by platelet-derived growth factor (PDGF), insulin, and hepatocyte growth factor/scatter factor (HGF/SF) receptor tyrosine kinases.
- Investigation of annexins as targets for protein kinase C (PKC) and cAMP-dependent protein kinase A (PKA).
Main Results:
- Annexin I and annexin II are major substrates for EGF-R and pp60v-src.
- Annexins are phosphorylated by multiple receptor tyrosine kinases and serine/threonine kinases.
- Phosphorylation is hypothesized to affect annexin's vesicle aggregation and phospholipid binding properties.
Conclusions:
- Annexin phosphorylation by diverse kinases is a significant regulatory mechanism.
- Understanding annexin phosphorylation is key to defining their precise physiological functions.
- Annexins' roles as kinase inhibitors also contribute to cellular signaling networks.