Protein kinase C isoenzymes: a review of their structure, regulation and role in regulating airways smooth muscle tone and mitogenesis

Webb, Benjamin L. J.; Hirst, Stuart J John; Giembycz, Mark A.

doi:10.1038/sj.bjp.0703452

Cited by 154 publications

(151 citation statements)

References 251 publications

(331 reference statements)

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…Protein kinase C is a multifunctional protein kinase that phosphorylates serine and threonine residues in many target proteins (Webb et al, 2000; …”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C Delta Cleavage Initiates an Aberrant Signal Transduction Pathway after Cardiac Arrest and Oxygen Glucose Deprivation

Raval

Dave

Prado

et al. 2005

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. dPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted dPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced dPKC translocation and increased its cleavage at 3 h of reperfusion. Since dPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either dPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of dPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote dPKC translocation/cleavage.

show abstract

“…Protein kinase C is a multifunctional protein kinase that phosphorylates serine and threonine residues in many target proteins (Webb et al, 2000; …”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C Delta Cleavage Initiates an Aberrant Signal Transduction Pathway after Cardiac Arrest and Oxygen Glucose Deprivation

Raval

Dave

Prado

et al. 2005

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…PKD was originally considered to be a member of the PKC family (1,2) but is now classified in the calcium/calmodulin-dependent kinase group based on sequence similarities in the kinase domain (3). The PKDs share a similar architecture consisting of a C-terminal catalytic domain, an N-terminal regulatory domain that encompasses two cysteine-rich regions (C1a and C1b), and a pleckstrin homology (PH) domain (4 -7).…”

mentioning

confidence: 99%

Protein Kinase D Induces Transcription through Direct Phosphorylation of the cAMP-response Element-binding Protein

Johannessen

Delghandi

Rykx

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Protein kinase D (PKD), a family of serine/threonine kinases, can be activated by a multitude of stimuli in a protein kinase C-dependent or -independent manner. PKD is involved in signal transduction pathways controlling cell proliferation, apoptosis, motility, and protein trafficking. Despite its versatile functions, few genuine in vivo substrates for PKD have been identified. In this study we demonstrate that the transcription factor cAMPresponse element-binding protein (CREB) is a direct substrate for PKD. PKD1 and CREB interact in cells, and activated PKD1 provokes CREB phosphorylation at Ser-133 both in vitro and in vivo. A constitutive active mutant of PKD1 stimulates GAL4-CREB-mediated transcription in a Ser-133-dependent manner, activates CRE-responsive promoters, and increases the expression of CREB target genes. PKD1 also enhances transcription mediated by two other members of the CREB family, ATF-1 and CREM. Our results describe a novel mechanism for PKD-induced signaling through activation of the transcription factor CREB and suggest that stimulus-induced phosphorylation of CREB, reported to be mediated by protein kinase C, may involve downstream activated PKD.The mammalian PKD 3 family of serine/threonine kinases includes the isoforms PKD1 (mouse PKD and human PKC), PKD2, and PKD3 (also named PKC). PKD was originally considered to be a member of the PKC family (1, 2) but is now classified in the calcium/calmodulin-dependent kinase group based on sequence similarities in the kinase domain (3). The PKDs share a similar architecture consisting of a C-terminal catalytic domain, an N-terminal regulatory domain that encompasses two cysteine-rich regions (C1a and C1b), and a pleckstrin homology (PH) domain (4 -7). A comparison of the amino acid sequences of PKD1-3 reveals that the highest homology lies in the catalytic domain, followed by C1a, C1b, and PH domain, suggesting that isoform-specific functions may be due to the regulatory part of the kinase (8).PKD1 can be activated by several mechanisms. The most studied mechanism involves a sequential activation of phospholipase C that results in the generation of the second messengers inositol 1,4,5-triphosphate and diacylglycerol (DAG) and subsequent activation of the classical (␣, ␤I, ␤II, and ␥) and novel (␦, ⑀, , and ) PKC isoforms. Binding of DAG to the C1b domain of PKD1 directs its translocation to the plasma membrane where activated novel PKC phosphorylates PKD1 at Ser-744/748 in the activation loop, causing activation of the enzyme. The activated enzyme can be imported via its C1b motif into the nucleus, where it transiently accumulates before being exported to the cytosol through a CRM1-dependent nuclear export pathway that requires the PH domain of PKD (4 -7). Mutations and deletions in the regulatory domain induce activation of PKD to various extents, and the entire regulatory domain has an inhibitory effect on the kinase activity (9). Indeed, PKD can also be activated through caspase-mediated cleavage of the regulatory domain (10). G␤␥ subunits ...

show abstract

“…The atypical group (aPKC) (/ and ) cannot be activated by calcium or DAG. All PKC family members bind PS on the cytosolic leaflet of the cell membrane, but aPKCs require additional incompletely defined lipid activators (24). Another isoform, PKC (often called PKD in the mouse), does not fit into any of the major groups.…”

mentioning

confidence: 99%

“…A logical candidate for such a difference is protein kinase C (PKC), because we and others have shown that it is required for apoptotic cell clearance (11,23). PKC comprises a family of related serine/threonine kinases divided into three groups on the basis of structure and cofactor requirements (24). Activation of PKC requires phosphorylation on serines/threonines, displacement of its autoinhibitory pseudosubstrate domain, and translocation to specific cytoskeletal and intracellular membrane sites of action (25).…”

mentioning

confidence: 99%

Activation of Protein Kinase C βII by the Stereo-specific Phosphatidylserine Receptor Is Required for Phagocytosis of Apoptotic Thymocytes by Resident Murine Tissue Macrophages

Todt¹,

Hu²,

Punturieri³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

We showed previously that protein kinase C (PKC) is required for phagocytosis of apoptotic leukocytes by murine alveolar (AMø) and peritoneal macrophages (PMø) and that such phagocytosis is markedly lower in AMø compared with PMø. In this study, we examined the roles of individual PKC isoforms in phagocytosis of apoptotic thymocytes by these two Mø populations. By immunoblotting, AMø expressed equivalent PKC but lower amounts of other isoforms (␣, ␤I, ␤II, ␦, ⑀, , and ), with the greatest difference in ␤II expression. A requirement for PKC ␤II for phagocytosis was demonstrated collectively by phorbol 12-myristate 13-acetate-induced depletion of PKC ␤II, by dose-response to PKC inhibitor Ro-32-0432, and by use of PKC ␤II myristoylated peptide as a blocker. Exposure of PMø to phosphatidylserine (PS) liposomes specifically induced translocation of PKC ␤II and other isoforms to membranes and cytoskeleton. Both AMø and PMø expressed functional PS receptor, blockade of which inhibited PKC ␤II translocation. Our results indicate that murine tissue Mø require PKC ␤II for phagocytosis of apoptotic cells, which differs from the PKC isoform requirement previously described in Mø phagocytosis of other particles, and imply that a crucial action of the PS receptor in this process is PKC ␤II activation.

show abstract

Protein kinase C isoenzymes: a review of their structure, regulation and role in regulating airways smooth muscle tone and mitogenesis

Cited by 154 publications

References 251 publications

Protein Kinase C Delta Cleavage Initiates an Aberrant Signal Transduction Pathway after Cardiac Arrest and Oxygen Glucose Deprivation

Protein Kinase C Delta Cleavage Initiates an Aberrant Signal Transduction Pathway after Cardiac Arrest and Oxygen Glucose Deprivation

Protein Kinase D Induces Transcription through Direct Phosphorylation of the cAMP-response Element-binding Protein

Activation of Protein Kinase C βII by the Stereo-specific Phosphatidylserine Receptor Is Required for Phagocytosis of Apoptotic Thymocytes by Resident Murine Tissue Macrophages

Contact Info

Product

Resources

About