| Research Abstract |
We have isolated cDNA clones encoding a new PKC family member PKC lambda. PKC lambda shows closest amino acid sequence identity with PKCzata(70% in total) and is structurally classified into the third sub-family of PKC. Expression of cDNAs for PKCzata and lambda in COS cells revealed the similarity in their biochemical properties in that both on them do not possess phorbol ester binding activities and that their kinase activities are not dependent on Ca, diacylglycerols, and phorbol esters. These structural and biochemical properties of PKCzata and lambda indicates that they are not the cellular receptor to diacylglycerols nor phorbol esters. Thus this subfamily is termed as aPKC (atypical PKC) subfamily.
In order to examine the functional differences of aPKC (zata, lambda) from conventional cPKC (alpha,beta,gamma) and from nPKC (delta,epsilon,eta,rheta), the effect of the overexpression of each of the members on the transcriptional activation of several cis-acting elements were examined. Overexpression of aPKC resulted in an enhancement of the transcriptional activation of TPA-response element (TRE) in response to serum but not TPA. Overexpression of cPKC or nPKC resulted in an enhanced transcriptional activation of a TPA-response element in response to TPA.
The results clearly indicate that aPKC is a novel family of signal transducing protein kinases which transmit a signal to TRE. Furthermore, the mode of the activation of aPKC differs from cPKC and nPKC. Further experiments to identify the serum factor which activates aPKC revealed that aPKC is activated in cells in response to tyrosine-kinase receptor activation implying the presence of a novel signaling pathway in cells from Tyr-kinase receptor to aPKC activation.
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