- •Protein phosphorylation as a switch in cellular functioning
- •Cyclic AMP and the amplification of signals
- •Protein kinase A
- •Protein kinase A and the regulation of transcription
- •Activation of the CREB transcription factor
- •Attenuation of the cAMP response elements by dephosphorylation
- •Protein kinase A and the activation of ERK
- •Actions of cAMP not mediated by PKA
- •Regulation of ion channels by cyclic nucleotides
- •Epac, a guanine nucleotide exchange factor directly activated by cAMP
- •Protein kinase C
- •Discovery of a phosphorylating activity independent cAMP
- •The protein kinase C family
- •Structural domains and activation of protein kinase C
- •The C1–C4 regions
- •Activation of protein kinase C
- •Multiple sources of diacylglycerol and other lipids activate protein kinase C
- •Differential localization of PKC isoforms
- •Different types of PKC-binding proteins
- •Holding back the PKC response
- •A matter of life or death: PKC signalling complexes in the evasion of the fly-swat
- •Phorbol ester and inflammation
- •References
Signal Transduction
FIG 9.8 The family of protein kinases C. Mammalian PKC comprises a family of nine distinct members subdivided, on the basis of their modes of activation, into three subfamilies: conventional (c), novel (n), and atypical (a). They are identified as PKC by the conserved domains C1, C2, C3, and C4. The protein is made up of regulatory and catalytic domains, connected by a hinge region. cPKC 1 and 2 are splice variants of the same gene. An alternative transcript exists for PKC which only encodes the catalytic domain and is referred to as PKM (not shown). We return to the matter of communication of atypical
PKCs with Par-6, p62, and Dsh on page 585.
The protein kinase C family
Molecular cloning has revealed a family of 9 genes giving rise to 11 distinct enzymes.45,46 Not all of these are activated by phorbol esters.47 They can be subdivided into three sub-families (see Table 9.1 and Figure 9.8). In addition, there are more distantly related enzymes such as PKC-related kinase (PRK, alternatively PKN),48 not considered here. The various isoforms are also referred to as isozymes, but this term is better reserved for an enzyme such as lactate dehydrogenase, since the isoforms of PKC have separate and characteristic substrates.
Table 9.1 PKC isoforms
Subfamily |
Isoforms |
Requirements for |
|
|
activation |
|
|
|
Conventional (cPKC) |
, 1, 2, |
DAG, PS, Ca2 |
Novel (nPKC) |
, , , |
DAG, PS |
|
|
|
Atypical (aPKC) |
, (human)/ (mouse) |
PS |
|
, (PKD) |
|
DAG, diacylglycerol; PS, phosphatidylserine.
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