Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282756
Title: Protein regulators of kinase C
Author: Robinson, Karen Ann
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1994
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Abstract:
Protein Kinase C (PKC) is a family of serine/threonine kinases. The PKC isoforms differ in distribution, substrate and cofactor specificity. This suggests that different isoforms may control different physiological events. The PKC family has a pivotal role in signal transduction, therefore its activity must be tightly regulated. The 14-3-3 family consists of highly conserved protein isoforms, with wide range of putative functions. The most abundant mammalian brain 14-3-3 isoforms inhibited PKC, within a three-fold range. Therefore regions conserved between 14-3-3 isoforms must contain the major PKC interaction sites, and variable 14-3-3 sites must also influence potency of inhibition. Individual PKC isoforms were inhibited by mixed brain 14-3-3 isoforms, with varying potency. This work enabled the primary 14-3-3 interaction site on PKC to be narrowed down to the conserved cysteine-rich region (C1). This was substantiated by evidence that diacylglycerol and phorbol ester, both of which bind the C1 region, interfere with inhibition by 14-3-3. Other proteins share this cysteine-rich region, for example c- raf-1, n-chimaerin, DAG kinase and phospholipase A2(PLA2). However 14-3-3 was unable to modify the activity of PLA2, and 14-3-3 had no PLA2 activity. PKCI (protein kinase C inhibitor), was originally purified from bovine brain. In this study a maize gene similar to bovine PKCI was expressed in E. coli, and purified to homogeneity. Maize and bovine PKCI shared characteristics: similar secondary structure, dimerism, and zinc-binding. However maize PKCI poorly inhibited PKC activity by a maximum of 20[percent]. In the presence of both 14-3-3 and maize PKCI, the effects on PKC were synergistic. Database searches have revealed that PKCI belongs to a new protein family, which share the novel zinc binding site.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.282756  DOI: Not available
Keywords: Biochemistry
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