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Regulation of growth factor-induced signaling by protein-tyrosine-phosphatases
J C Byon1, K A Kenner, A B Kusari
1Department of Physiology, Tulane University Medical Center, New Orleans, Louisiana 70112-2699, USA.
Abstract:
The binding of a growth factor to its specific receptor catalyzes a complex cascade of intracellular signaling events, characterized by changes in the phosphorylation state of many key proteins. Among these phosphorylation events, tyrosine phosphorylation plays a prominent role in the transmission of postreceptor signals. The state of tyrosine phosphorylation is regulated by the actions of protein-tyrosine kinases (PTKs) and protein-tyrosine-phosphatases (PTPs). Dysregulation of either event can lead to abnormal cellular responses. PTPs generally act to regulate negatively-that is, to turn off-any signals generated by PTKs. However, this is not always the case, as seen by the phosphatase SHP-2, which can either be a positive or negative regulator of signal transduction depending on the particular cellular context. In addition, a novel family of dual specificity phosphatases has been recently discovered. These enzymes are capable of dephosphorylating phosphotyrosine and phosphothreonine/phosphoserine residues, and seem to play a significant role in attenuating the action of MAP kinases. Several themes appear throughout PTP regulation of growth factor signaling, including positive or negative regulation, importance of cell/ tissue type, identity of the receptor activated, and subcellular localization. Although only a handful of PTPs have been identified, the present work done in elucidating their function has revealed their significance in the maintenance of normal physiological responses to growth factors.
Insights
Protein-tyrosine phosphatases (PTPs) regulate growth factor signaling by controlling tyrosine phosphorylation. Their diverse roles, including positive or negative regulation, are crucial for normal cellular responses.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Signaling
Background:
- Growth factor receptor binding initiates intracellular signaling cascades involving protein phosphorylation.
- Tyrosine phosphorylation is a key mechanism in postreceptor signal transmission.
- Protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) regulate tyrosine phosphorylation states.
Purpose of the Study:
- To elucidate the multifaceted roles of PTPs in regulating growth factor signaling.
- To highlight the significance of PTPs in maintaining normal physiological responses.
- To discuss the regulatory mechanisms and contextual influences on PTP activity.
Main Methods:
- Review of existing literature on PTPs and growth factor signaling.
- Analysis of PTP mechanisms, including dual specificity phosphatases.
- Examination of factors influencing PTP function, such as cell type and localization.
Main Results:
- PTPs can act as either negative or positive regulators of signal transduction, exemplified by SHP-2.
- Dual specificity phosphatases dephosphorylate multiple residues and attenuate MAP kinase signaling.
- PTP regulation is context-dependent, influenced by cell type, receptor, and subcellular localization.
Conclusions:
- PTPs are critical regulators of growth factor signaling pathways.
- Understanding PTP function is essential for comprehending normal physiological responses.
- Despite a limited number of identified PTPs, their importance in cellular signaling is well-established.