The C2 domain acts as a Ca2+ sensor and can be found in conventional and novel isoforms. However, the C1 domain in atypical PKCs cannot bind to DAG or phorbol esters. This domain is functional and can bind DAG in both conventional and novel isoforms. The C1 domain has a binding site for DaG and non-hydrolysable, non-physiological analogues known as phorbol esters. The regulatory domain of PKCs contains multiple subregions that are shared. Due to its similarity to other kinases with documented crystal structures, there have been many predictions. The exception to this is PKC theta and iota. Much of the crystal structure of the catalytic region of PKC has yet to be determined. The second messenger requirement in isoforms differs due to the regulatory region. The catalytic region is highly conserved among the different isoforms and the catalytic region of other serine/threonine kinases. Protein Kinase-C often refers to the entire family of isoforms.Īll PKCs have a regulatory and catalytic domain that is tethered via a hinge region. This means that conventional and novel PKCs are activated through the same signal transduction pathway as phospholipase C.Ītypical PKCs (including protein kinase Mζ and ι / λ isoforms) don’t require Ca2+ or diacylglycerol for activation. However, they do not require Ca2+ for activation. Novel PKCs include the δ, ε, η, and θ isoforms and require DAG. They need DAG, Ca2+, and a phospholipid such as phosphatidylserine for activation.
This is conventional (or classical), novel and atypical.Ĭonventional PKCs contain the isoforms α, βI, βII, and γ. That PKC family consists of fifteen isozymes in humans that are split into three subfamilies based on their second messenger requirements. This makes PKC enzymes important in several signal transduction cascades. The PKC enzymes are activated by signals such as the increased concentration of diacylglycerol levels or calcium ions. These observations would rule out the possibility that the site specificity of CK2 might overlap with that of cdc2 and possibly of other Pro-directed protein kinases.Protein Kinase-C (also known as PKC) is a family of protein kinase enzymes that are involved in controlling the function of other proteins via the phosphorylation of hydroxyl groups of serine and threonine amino acid residues. Moreover the motif Ser-Pro is detrimental for CK2, preventing the phosphorylation of otherwise suitable peptides. Such a requirement for a basic residue at position +3 is opposite to that of CK2 whose consensus sequence (S-X-X-E/D/Yp/Sp) includes an acidic residue at the same position. Thus the consensus sequence for cdc2 is shown to be X-S-P-X-K. The individual substitutions of Pro-5 and Lys-7 in the latter peptide with Gly and Ala (or Glu), respectively, prevent its phosphorylation by cdc2, whereas the substitution of Lys-3 with Ala is well tolerated and the substitution of the target Ser with Thr actually improves phosphorylation. The opposite is true of the C-terminal peptide beta(206-215), NFKSPVKTIR, whose Ser-4 is a good target for cdc2 while being unaffected by CK2. The N-terminal peptide beta(1-9), MSSSEEVSW, is readily phosphorylated by CK2 but not all by cdc2.
#Kinases with known consensus sequences series
Two series of synthetic peptides that reproduce the amino- and carboxyl-terminal segments of the beta-subunit of casein kinase-2, including the sites phosphorylated by CK2 and cdc2 kinase, respectively, have been used as model substrates for these enzymes.
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