Limits...
Cell signaling through protein kinase C oxidation and activation.

Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR - Int J Mol Sci (2012)

Bottom Line: In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events.The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues.These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil; E-Mails: rocco@bioqmed.ufrj.br (N.R.-M.); meyer@bioqmed.ufrj.br (J.R.M.-F.) ; Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.

ABSTRACT
Due to the growing importance of cellular signaling mediated by reactive oxygen species (ROS), proteins that are reversibly modulated by these reactant molecules are of high interest. In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events. The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues. Protein kinase C (PKC) is involved in a variety of cellular signaling pathways. These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification. A large number of scientific studies have highlighted the importance of ROS as a second messenger in numerous cellular processes, including cell proliferation, gene expression, adhesion, differentiation, senescence, and apoptosis. In this context, the goal of this review is to discuss the mechanisms by which PKCs are modulated by ROS and how these processes are involved in the cellular response.

No MeSH data available.


Related in: MedlinePlus

Schematic sequence of protein kinase C (PKC) isozymes indicating the domain structure of the PKC subfamilies and their respective activators.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC3472709&req=5

f1-ijms-13-10697: Schematic sequence of protein kinase C (PKC) isozymes indicating the domain structure of the PKC subfamilies and their respective activators.

Mentions: The PKC family is composed of serine/threonine protein kinases that are involved in a variety of pathways that regulate cell growth, differentiation, apoptosis, transformation and tumorigenicity. Most cells express more than one isoform, and each type of PKC mediates different cellular events [8,9]. The various PKC isoforms consist of NH2-terminal regulatory domains and COOH-terminal catalytic domains [10]. They also have in common the pseudosubstrate site (PS), which keeps the protein in its inactive form [11]. However, they differ in their structure, cofactor requirement and substrate specificity [11]. Thus, the 10 members of the PKC family have been divided into three major groups: the classical PKCs (cPKCs), including the α, βI, βII, and γ isoforms; the novel PKCs (nPKCs), including the θ, η, ɛ, δ isoforms; and the atypical PKCs (aPKCs), including the ζ and ι/λ isoforms [12–14]. The cPKC subfamily members possess conserved (C1–C4) and variable (V1–V5) regions, which are presented in Figure 1 [11,12]. They require calcium, phosphatidylserine and diacylglycerol (DAG) or phorbol esters for activation. The nPKCs differ from cPKCs in that they lack the C2 homologous domain and do not require calcium for activation. Finally, aPKCs lack both the C2 and half of the C1 homologous domains, thus rendering them insensitive to DAG, phorbol esters, and calcium [10,15]. Figure 1 depicts the three classes of PKCs and their respective activators. PKCμ and PKCυ isorforms are now classified as members of the DAG receptor protein kinase D (PKD), which is a family of serine/threonine protein kinases classified as a subfamily of the Ca2+/calmodulin-dependent kinase (CaMK) superfamily. For a complete review of PKD see [16,17].


Cell signaling through protein kinase C oxidation and activation.

Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR - Int J Mol Sci (2012)

Schematic sequence of protein kinase C (PKC) isozymes indicating the domain structure of the PKC subfamilies and their respective activators.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472709&req=5

f1-ijms-13-10697: Schematic sequence of protein kinase C (PKC) isozymes indicating the domain structure of the PKC subfamilies and their respective activators.
Mentions: The PKC family is composed of serine/threonine protein kinases that are involved in a variety of pathways that regulate cell growth, differentiation, apoptosis, transformation and tumorigenicity. Most cells express more than one isoform, and each type of PKC mediates different cellular events [8,9]. The various PKC isoforms consist of NH2-terminal regulatory domains and COOH-terminal catalytic domains [10]. They also have in common the pseudosubstrate site (PS), which keeps the protein in its inactive form [11]. However, they differ in their structure, cofactor requirement and substrate specificity [11]. Thus, the 10 members of the PKC family have been divided into three major groups: the classical PKCs (cPKCs), including the α, βI, βII, and γ isoforms; the novel PKCs (nPKCs), including the θ, η, ɛ, δ isoforms; and the atypical PKCs (aPKCs), including the ζ and ι/λ isoforms [12–14]. The cPKC subfamily members possess conserved (C1–C4) and variable (V1–V5) regions, which are presented in Figure 1 [11,12]. They require calcium, phosphatidylserine and diacylglycerol (DAG) or phorbol esters for activation. The nPKCs differ from cPKCs in that they lack the C2 homologous domain and do not require calcium for activation. Finally, aPKCs lack both the C2 and half of the C1 homologous domains, thus rendering them insensitive to DAG, phorbol esters, and calcium [10,15]. Figure 1 depicts the three classes of PKCs and their respective activators. PKCμ and PKCυ isorforms are now classified as members of the DAG receptor protein kinase D (PKD), which is a family of serine/threonine protein kinases classified as a subfamily of the Ca2+/calmodulin-dependent kinase (CaMK) superfamily. For a complete review of PKD see [16,17].

Bottom Line: In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events.The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues.These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil; E-Mails: rocco@bioqmed.ufrj.br (N.R.-M.); meyer@bioqmed.ufrj.br (J.R.M.-F.) ; Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.

ABSTRACT
Due to the growing importance of cellular signaling mediated by reactive oxygen species (ROS), proteins that are reversibly modulated by these reactant molecules are of high interest. In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events. The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues. Protein kinase C (PKC) is involved in a variety of cellular signaling pathways. These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification. A large number of scientific studies have highlighted the importance of ROS as a second messenger in numerous cellular processes, including cell proliferation, gene expression, adhesion, differentiation, senescence, and apoptosis. In this context, the goal of this review is to discuss the mechanisms by which PKCs are modulated by ROS and how these processes are involved in the cellular response.

No MeSH data available.


Related in: MedlinePlus