Chemistry: molecular biology and microbiology – Spore forming or isolating process
Patent
1994-12-02
1997-01-21
Hendricks, Keith D.
Chemistry: molecular biology and microbiology
Spore forming or isolating process
435194, 4353201, 4352523, 4352402, 4352404, 536 232, C12N 510, C12N 912, C12N 1554
Patent
active
055959024
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a novel protein, compounds useful for the regulation of the activity of such protein, screening methods for identifying such compounds, the use of such protein and compounds in medicine, end to DNA sequences encoding the protein.
Protein kinase C is the name given to a family of enzymes that contain a regulatory unit with a binding site for phospholipid or diacylglycerol and a catalytic unit containing an ATP binding site. Some members of the family also contain a Ca.sup.2+ binding site. The enzymes are important regulatory proteins in the signal transduction process by which the cells respond to signals received at cell surface receptors. Typically, protein kinase C is activated by diacylglycerol released from the action of phospholipase C on phosphatidylinositol (PIP.sub.2). Binding of diacylglycerol to protein kinase C in the presence of ATP results in activation of the protein kinase C and it can then phosphorylate other enzymes involved in metabolic processes thereby regulating the metabolic processes. The specificity of the protein substrate for phosphorylation by protean kinase C is dependent on the particular isoform.
Several isoforms of protein kinase C have already been identified and these have been given the subscripts alpha, beta, beta II, gamma, delta, epsilon and zeta. We have now identified a further, novel isoform of protein kinase C which differs from the zeta isoform chiefly in the amino terminal region--a region believed to be important in the determination of substrate specificity.
The novel protein kinase C of the present invention is named protean kinase C (iota). The deduced amino acid sequence of the novel protein suggests that it is atypical protein kinase C which is most probably not activated by diacylglycerol derived from PIP.sub.2. The mRNA encoding for the novel protein has been shown to be present in hamster insulinoma cells (HIT cells) and rat insulinoma cells (RIN) and also in isolated pancreatic islets from rats. Its presence in these cell lines and pancreatic islets suggests that it is involved in the regulation of the activity of hormones that originate in the pancreatic islets and are involved in the control of glycaemia, for example hormones such as insulin, glucagon and amylin. This is especially true of the capacity of glucose and other nutrients to stimulate the release of these hormones, since the nutrients generate diacylglycerol and other lipids, which might activate the novel protein, through pathways other than PIP.sub.2 breakdown. The regulation of the activity of protein kinase C (iota) is therefore considered to have important potential in the treatment of diabetes.
There is experimental evidence that the atypical protein kinase C zeta isoform is activated by certain growth factors. Our laboratory has now shown that protein kinase C iota binds to another protein, ras-GAP, which is known to act in the chain of events initiated by growth factors that act on receptor tyrosine kinase. The regulation of the activity of protein kinase C iota is therefore considered to have important potential in the treatment of cancer.
Accordingly, in a first aspect the present invention consists in a DNA molecule which encodes human protein kinase C (iota), the DNA molecule having a sequence substantially as shown in Table 1 or a complementary sequence or a sequence which hybridizes thereto under stringent conditions.
Also provided are a vector comprising such a sequence, a host cell transformed with such a vector and recombinant proteins encoded for such a sequence.
In a second aspect the present invention consists in a method of producing protein kinase C (iota) comprising culturing the cell including the DNA molecule of the first aspect of the present invention under conditions which allow expression of the DNA molecule encoding human protein kinase C (iota) and recovering the expressed protein kinase C (iota).
In a third aspect the present invention consists in human protein kinase C (iota) in a substantially pure form.
In a fourth aspect th
REFERENCES:
Liyanage et al., Biochem. J., vol. 283: 781-787 1992.
Selbie et al., J. Biol. Chem., vol. 268, No. 32, pp. 24296-24302, iss. Nov. 15, 1993.
Goodnight et al., Gene, vol. 122, pp. 305-311 1992.
Biden Trevor J.
Selbie Lisa
Garvan Institute of Medical Research
Hendricks Keith D.
LandOfFree
DNA encoding human protein kinase C (iota) does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with DNA encoding human protein kinase C (iota), we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and DNA encoding human protein kinase C (iota) will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2323546