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Control of genetically prescribed protein tyrosine kinase activities by environment-linked redox reactions.

ABSTRACT: Recent observations on environment-linked control of genetically prescribed signaling systems for either cell activation or cell death have been reviewed with a focus on the regulation of activities of protein tyrosine kinases (PTKs). The environment-linked redox reactions seem to primarily affect cell surface receptors and cell membrane lipid rafts, and they induce generation of reactive oxygen species (ROS) in cells. ROS thus generated might upregulate the catalytic activities of PTKs through inactivating protein tyrosine phosphatases that dephosphorylate and inactivate autophosphorylated PTKs. Recent evidence has, however, demonstrated that ROS could also directly oxidize SH groups of genetically conserved specific cysteines on PTKs, sometimes producing disulfide-bonded dimers of PTK proteins, either for upregulation or downregulation of their catalytic activities. The basic role of the redox reaction/covalent bond-mediated modification of protein tertiary structure-linked noncovalent bond-oriented signaling systems in living organisms is discussed.

SUBMITTER: Nakashima I

PROVIDER: S-EPMC3132499 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Control of genetically prescribed protein tyrosine kinase activities by environment-linked redox reactions.

Nakashima Izumi I Kawamoto Yoshiyuki Y Takeda Kozue K Kato Masashi M

Enzyme research 20110626

Recent observations on environment-linked control of genetically prescribed signaling systems for either cell activation or cell death have been reviewed with a focus on the regulation of activities of protein tyrosine kinases (PTKs). The environment-linked redox reactions seem to primarily affect cell surface receptors and cell membrane lipid rafts, and they induce generation of reactive oxygen species (ROS) in cells. ROS thus generated might upregulate the catalytic activities of PTKs through ...[more]

PMID: 21755044

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Project description:Anaplastic lymphoma kinase (ALK) rearrangements occur in ∼3%-6% of patients with advanced non-small-cell lung cancer (NSCLC). Small molecular drugs that effectively inhibit ALK gene have revolutionized the therapeutic paradigm for patients with ALK rearrangements, resulting in significant improvements in objective response rate, progression-free survival, and overall survival compared with classical platinum-based chemotherapy. Several ALK tyrosine kinase inhibitors (ALK-TKIs), including crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib, have been recommended as standard first-line treatment for advanced NSCLC patients with ALK rearrangements. Patients with ALK rearrangements typically exhibit long-term durable responses to ALK-TKIs; therefore, the management of adverse drug reactions (ADRs) with ALK-TKIs is crucial in clinical practice to maximize clinical benefits, prevent an adverse impact on quality of life, and improve patient compliance. In general, ALK-TKIs are well tolerated. There are, however, a number of serious toxicities that may necessitate dose modification or even discontinuation of treatment and the management of ADRs with ALK-TKIs has grown in importance. The therapeutic use of this class of medications still carries some risk because there are currently no pertinent guidelines or consensus recommendations for managing ADRs caused by ALK-TKIs in China. In order to improve the clinical management of ADRs with ALK-TKIs, the Chinese Society of Clinical Oncology (CSCO) Non-small Cell Lung Cancer Professional Committee led the discussion and summary of the incidence, diagnosis and grading standards, and prevention and treatment of ADRs caused by ALK-TKIs. Highlights • Though ALK-TKIs are well tolerated, certain toxicities may necessitate dosage adjustments or treatment cessation.• The management of ADRs with ALK-TKIs has grown in importance.• The CSCO NSCLC Professional Committee led the expert consensus of management of ADRs with ALK-TKIs.• The current consensus can help in improving the clinical management of ADRs with ALK-TKIs.

Dataset Information

Control of genetically prescribed protein tyrosine kinase activities by environment-linked redox reactions.

Publications

Control of genetically prescribed protein tyrosine kinase activities by environment-linked redox reactions.

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