Biomedical subjects

C Sugden

Publications and source records attributed to C Sugden.

5 recordsLinked to original sources

PubMed1999

Regulation of spinach SNF1-related (SnRK1) kinases by protein kinases and phosphatases is associated with phosphorylation of the T loop and is regulated by 5'-AMP.

Members of the SNF1-related protein kinase-1 (SnRK1) subfamily of protein kinases are higher plant homologues of mammalian AMP-activated and yeast SNF1 protein kinases. Based on analogies with the mammalian system, we surmised that the SnRK1 kinases would be regulated by phosphorylation on a threonine [equivalent to Thr175 in Arabidopsis thaliana SnRK1 (AKIN10)] within the 'T loop' between the conserved DFG and APE motifs. We have raised an antibody against a phosphopeptide based on this sequence, and used it to show that inactivation of two spinach SnRK1 kinases by protein phosphatases, and reactivation by a mammalian upstream protein kinase, is associated with changes in the phosphorylation state of this threonine. We also show that dephosphorylation of this threonine by protein phosphatases, and consequent inactivation, is inhibited by low concentrations of 5'-AMP, via binding to the substrate (i.e. the kinase). This is the first report showing that the plant SnRK1 kinases are regulated by AMP in a manner similar to their mammalian counterparts. The possible physiological significance of these findings is discussed.

AMP-Activated Protein Kinases↗

PubMed1999

Two SNF1-related protein kinases from spinach leaf phosphorylate and inactivate 3-hydroxy-3-methylglutaryl-coenzyme A reductase, nitrate reductase, and sucrose phosphate synthase in vitro.

We resolved from spinach (Spinacia oleracea) leaf extracts four Ca2+-independent protein kinase activities that phosphorylate the AMARAASAAALARRR (AMARA) and HMRSAMSGLHLVKRR (SAMS) peptides, originally designed as specific substrates for mammalian AMP-activated protein kinase and its yeast homolog, SNF1. The two major activities, HRK-A and HRK-C (3-hydroxy-3-methylglutaryl-coenzyme A reductase kinase A and C) were extensively purified and shown to be members of the plant SnRK1 (SNF1-related protein kinase 1) family using the following criteria: (a) They contain 58-kD polypeptides that cross-react with an antibody against a peptide sequence characteristic of the SnRK1 family; (b) they have similar native molecular masses and specificity for peptide substrates to mammalian AMP-activated protein kinase and the cauliflower homolog; (c) they are inactivated by homogeneous protein phosphatases and can be reactivated using the mammalian upstream kinase; and (d) they phosphorylate 3-hydroxy-3-methylglutaryl-coenzyme A reductase from Arabidopsis at the inactivating site, serine (Ser)-577. We propose that HRK-A and HRK-C represent either distinct SnRK1 isoforms or the same catalytic subunit complexed with different regulatory subunits. Both kinases also rapidly phosphorylate nitrate reductase purified from spinach, which is associated with inactivation of the enzyme that is observed only in the presence of 14-3-3 protein, a characteristic of phosphorylation at Ser-543. Both kinases also inactivate spinach sucrose phosphate synthase via phosphorylation at Ser-158. The SNF1-related kinases therefore potentially regulate several major biosynthetic pathways in plants: isoprenoid synthesis, sucrose synthesis, and nitrogen assimilation for the synthesis of amino acids and nucleotides.

Amino Acid Sequence↗

PubMed1996

Student debt: an inevitable problem?

Since the government introduced the loan scheme for university students in 1990, it has become abundantly apparent that students are falling increasingly into debt. This paper describes the results of two studies undertaken by Manchester undergraduate dental students into the level and consequences of debt on dental students.

Education, Dental↗

PubMed1995

Student debt.

Explore the source record for details and available documents.

Education, Dental↗

PubMed1994

Speed of onset of sensory block for elective extradural caesarean section: choice of agent and temperature of injectate.

We have studied the effects of choice of local anaesthetic and temperature of extradural injectate on speed of onset of sensory block for elective extradural Caesarean section in a double-blind trial in 120 women allocated randomly to one of four groups to receive either plain 0.5% bupivacaine or 2% lignocaine with 1:200,000 adrenaline at either room temperature or 38 degrees C. The onset time of lignocaine with adrenaline was shorter than that of bupivacaine regardless of temperature (P < 0.01). Warmed lignocaine produced the most rapid block overall (P < 0.025). The incidence of hypotension, ephedrine requirement, shivering, quality of analgesia and additional analgesic requirements were similar for all groups.

Anesthesia, Epidural↗