Objective
Protein kinase C (PKC) is a multi-domain serine/threonine kinase that is activated by diacylglycerol (DAG), a short-lived derivative of phosphatidylinositol, 4,5-biphosphate (PIP2) and phorbol esters. The kinase activity of PKC is regulated by its N-terminal region that contains the binding sites for DAG and phorbol esters (C1 domain) and Ca2+ and phospholipids (C2 domain). The PKC family includes several isozymes which define two distinct groups; the Ca2+-dependent (cPKCs) and the Ca2+-independent (nPKCs). The inability of nPKCs to be regulated by Ca2+ has been attributed to the absence of a classical C2 domain. We have recently expressed large quantities of a C2-like domain of a novel PKC (nPKC) in E. coli . We have successfully obtained crystals of this domain suitable for X-ray analysis. We therefore intend to determine the structure of this domain. Moreover, there is recent evidence that this domain influences the interaction between PKC and one of its substrates (Dekker & Parker, data unpublished). Once the crystal structure of this domain has been determined, we will pursue co-crystallization trials of PKC bound to interacting peptides derived from the substrate. Individual domain structures provide an insight into the binding sites for activating ligands of PKC. However, they do not address the overall architecture of the full length molecule or the specific domain:domain interactions. Such interactions may ultimately define the mechanism of regulation of full length PKC. In parallel to our efforts with the C2-like domain, we intend to prepare constructs of the entire catalytic and regulatory domains and to produce such constructs in E. coli . Our current success with the C2-like domain, has encouraged these efforts. Moreover, full length novel PKC isozymes have become available to us from our collaborators (Dr. Peter Parker, ICRF) and attempts to obtain high quality crystals of the full length isozymes have been initiated. To conclude, the solution of the structure of a PKC C2-like domain will provide an additional component of the PKC structure. Moreover, the co-crystallisation trials with the substrate peptides will provide information on residues involved in the PKC:substrate interaction. Our efforts will also extend to studying constructs of consecutive PKC domains in addition to the full length protein with the hope that obtaining even a moderate resolution crystal structure of the full length molecule will provide an insight to the overall architecture and regulation of an essential part of the cell signalling machinery.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering crystals
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences biochemistry biomolecules proteins
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Data not available
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
WC2A 3PX London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.