SEARCH · PubMed Health

Results for “functionality”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

PubMed1986

Non invasive assessment of regional diastolic left ventricular function with first pass radionuclide functional imaging in ischaemic heart disease.

Functional images of regional distribution of rapid filling (RF) rates have been developed and applied at rest and on exercise for regional analysis of 301 coronary artery territories (103 compromised by coronary narrowings, 198 normal). The observed time-interval of RF averaged 209 ms at rest (range 200 to 280) and 172 ms on exercise (range 125 to 200 ms). Normal RF is directed to the apex, and it is deviated from territories with reduced compliance to normal territories. Sensitivity in detection and localization of territories compromised by coronary narrowings exceeds 90% at rest for the anterior and infero-posterior wall and is higher than that obtained from systolic functional images. Specificity amounts also to over 90% and is much higher than that observed with systolic functional images. During RF, moderate to severe loss in compliance results in initial regional paradoxical inward motion in 40 to 45% of anterior or postero-inferior segments eventually accompanied by significant inward displacement of blood. Thus, with functional imaging of regional RF rates one can establish dysfunction and functional significance of coronary narrowings.

Adult↗

PubMed2001

Phylogeny, function, and evolution of the cupins, a structurally conserved, functionally diverse superfamily of proteins.

The cupin superfamily is a group of functionally diverse proteins that are found in all three kingdoms of life, Archaea, Eubacteria, and Eukaryota. These proteins have a characteristic signature domain comprising two histidine- containing motifs separated by an intermotif region of variable length. This domain consists of six beta strands within a conserved beta barrel structure. Most cupins, such as microbial phosphomannose isomerases (PMIs), AraC- type transcriptional regulators, and cereal oxalate oxidases (OXOs), contain only a single domain, whereas others, such as seed storage proteins and oxalate decarboxylases (OXDCs), are bi-cupins with two pairs of motifs. Although some cupins have known functions and have been characterized at the biochemical level, the majority are known only from gene cloning or sequencing projects. In this study, phylogenetic analyses were conducted on the conserved domain to investigate the evolution and structure/function relationships of cupins, with an emphasis on single- domain plant germin-like proteins (GLPs). An unrooted phylogeny of cupins from a wide spectrum of evolutionary lineages identified three main clusters, microbial PMIs, OXDCs, and plant GLPs. The sister group to the plant GLPs in the global analysis was then used to root a phylogeny of all available plant GLPs. The resulting phylogeny contained three main clades, classifying the GLPs into distinct subfamilies. It is suggested that these subfamilies correlate with functional categories, one of which contains the bifunctional barley germin that has both OXO and superoxide dismutase (SOD) activity. It is proposed that GLPs function primarily as SODs, enzymes that protect plants from the effects of oxidative stress. Closer inspection of the DNA sequence encoding the intermotif region in plant GLPs showed global conservation of thymine in the second codon position, a character associated with hydrophobic residues. Since many of these proteins are multimeric and enzymatically inactive in their monomeric state, this conservation of hydrophobicity is thought to be associated with the need to maintain the various monomer- monomer interactions. The type of structure-based predictive analysis presented in this paper is an important approach for understanding gene function and evolution in an era when genomes from a wide range of organisms are being sequenced at a rapid rate.

Amino Acid Sequence↗

PubMed2001

Influence of admission functional status on functional change after stroke rehabilitation.

OBJECTIVE: To determine whether the admission functional score influences the functional change after stroke rehabilitation. DESIGN: Two hundred forty-three patients who had received the Functional Independence Measure (FIM) assessment at admission and at discharge were enrolled in the study. The patients were stratified into three groups according to their FIM total scores at admission, i.e., < or =36, 37 to 72, and > or =73. RESULTS: The Scheffé's multiple comparison test showed that patients with FIM total scores of > or =73 at admission were significantly younger (58 +/- 11 [SD] yr) than those who had scores of 37 to 72 (64 +/- 11 yr) or < or =36 (66 +/- 12 yr). Patients with FIM total scores of 37 to 72 at admission showed significantly higher FIM gain (37 +/- 15) compared with those patients who had scores of > or =73 (20 +/- 10) or < or =36 (29 +/- 23). CONCLUSION: The functional levels of affected patients at admission stratified by the FIM scale roughly predict the degree of functional gain after rehabilitation in survivors with a first episode of ischemic stroke. Moderately affected patients will benefit from intensive rehabilitation. These findings may be useful for rehabilitation triage.

Aged↗

PubMed1995

Mapping function in the human brain with magnetoencephalography, anatomical magnetic resonance imaging, and functional magnetic resonance imaging.

Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuro-imaging methods.

Brain↗

PubMed1997

Restoration of function in the paralyzed rabbit orbicularis oculi muscle by direct functional electrical stimulation.

Restoration of the ability to blink and protect the eye in the patient with facial paralysis remains a challenge. Although many treatments exist, no one approach corrects all the deficits associated with the loss of orbicularis oculi function. In this study, the author investigated the feasibility of restoring function by direct electrical stimulation of the paralyzed orbicularis oculi muscle in the rabbit model. Using a pacing device developed by the author, functional restoration of a normal-appearing blink was produced throughout 30 days of continuous pacing in six rabbits with transected facial nerves. Histologic evaluations of the paced tissues demonstrated no evidence of detrimental effects attributable to the electrical stimulation. The findings of this study support the feasibility of employing direct electrical stimulation to restore the function of paralyzed orbicularis oculi muscles. Potential applications may also exist in other areas in which peripheral denervation creates functional impairment.

Animals↗

PubMed2001

Exercise training, vascular function, and functional capacity in middle-aged subjects.

PURPOSE: The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. METHODS: After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. RESULTS: Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). CONCLUSION: These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.

Anthropometry↗

PubMed1999

Integration of functional magnetic resonance imaging supported by magnetoencephalography in functional neuronavigation

OBJECTIVE: In this study, the intraoperative visualization of functional data provided by functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) leading to functional neuronavigation is demonstrated in surgery around the motor strip. METHODS: In seven patients with lesions adjacent to the central region, fMRI was performed with a 1.5-Tesla magnetic resonance system, using axial echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI and MEG were matched to an anatomic three-dimensional magnetic resonance image set by a contour fit. Then this three-dimensional image data set was transferred to the navigation microscope and displayed in the eyepieces of the microscope during surgery. Additionally, intraoperative recording of somatosensory evoked potentials was performed for verification of the central sulcus. RESULTS: In all cases, the projection of fMRI and MEG data into the operating viewing field allowed easy identification of the central region, which was confirmed by phase reversal of somatosensory evoked potentials in each case. fMRI and MEG measurements yielded corresponding results in each patient. CONCLUSION: Functional neuronavigation with integration of fMRI and MEG allows the fast identification of eloquent brain areas. The widespread availability of fMRI will result in a broad availability of functional neuronavigation, which will, in turn, contribute to the successful surgery of lesions in eloquent brain areas with lower morbidity.

Journal Article↗

PubMed2000

An integrated functional magnetic resonance imaging procedure for preoperative mapping of cortical areas associated with tactile, motor, language, and visual functions.

OBJECTIVE: To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions. METHODS: Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6). RESULTS: For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results. CONCLUSION: This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

Adolescent↗

PubMed1983

Functional capacity and rehabilitation of recipients with a functioning renal allograft for ten years or more.

Forty-nine renal transplant recipients who had a single functioning allograft for ten or more years are reviewed. There were 17 cadaver recipients and 32 living-related recipients. Most patients have enjoyed excellent long-term renal function with stable mean daily dosages of azathioprine and prednisone. Fifty-three percent of patients never experienced a rejection episode, and 24% of patients experienced only one rejection episode. Five recipients (10%) developed malignancy following transplantation. Based on the Karnofsky activity scale, 80% of patients enjoyed unrestricted activity at ten years posttransplant. The two major factors contributing to declining activity were progression of systemic diseases such as atherosclerosis or diabetes, and declining allograft function. Following transplantation, all patients developed renewed interest in sexual activity, all men were potent, and all women experienced regular menses. Nine men achieved fatherhood and five women underwent successful pregnancy. Currently, 46 recipients are alive with a functioning allograft. These data confirm the ability of recipients with a long-term functioning renal allograft to return to the work force, participate in preillness levels of activity, and enjoy sexual activity and parenthood.

Activities of Daily Living↗

PubMed2002

Hypertension is an independent predictor of delayed graft function and worse renal function only in kidneys with chronic pathological lesions.

BACKGROUND: Delayed graft function (DGF) has been identified as one of the principal correlates of poor graft survival in cadaveric renal transplantation. However, its risk factors and clinical predictors have been poorly elucidated. METHODS: We analyzed the risk factors of DGF with a specific emphasis on the role of histological damage of donor kidney. Then, we also studied the impact of DGF, and donor factors affecting DGF, on kidney graft function over the first year after engraftment in 100 consecutive cadaveric renal transplant (Tx) recipients. RESULTS: The organs displaying DGF (n=48) had a significantly higher degree of glomerular sclerosis and tubular atrophy (P<0.01), as well as of interstitial fibrosis and vascular damage (P<0.02) in time-zero biopsies. In patients who received an "ideal" organ for Tx (total histological score < or = 4), DGF showed a strong relationship with Deltaage D-R (70% increase of risk for donors 10 years older than recipients), and with the histological score (odds ratio 1.34). In contrast, donor hypertension was the most relevant variable independently associated with DGF (odds ratio 19.4) in patients receiving a suboptimal organ (histological score >4). Moreover, DGF and donor hypertension adversely affected graft function at 1 year, but only in Tx patients with a histological score >4 in time-zero biopsy. Of note, both patients with and those without DGF showed a very low incidence of biopsy-proven acute rejection (8.5 and 6.8%, respectively) and a rather short cold ischemia time (<16 hr). CONCLUSION: Our findings suggest that the quality of the transplanted organ and the occurrence of DGF are strictly related to each other and can influence graft function through apparently nonimmune mechanisms. In addition, long-standing donor hypertension is a strong independent variable affecting both DGF and graft function of suboptimal cadaveric kidneys, at least up to 1 year.

Adult↗

PubMed2001

Partition functions in statistical mechanics, symmetric functions, and group representations.

Partition functions for noninteracting particles are known to be symmetric functions. It is shown that powerful group-theoretical techniques can be used not only to derive these relationships, but also to significantly simplify calculation of the partition functions for particles that carry internal quantum numbers. The partition function is shown to be a sum of one or more group characters. The utility of character expansions in calculating the partition functions is explored. Several examples are given to illustrate these techniques.

Journal Article↗

PubMed1991

Glycaemic thresholds for hypoglycaemic symptoms, impairment of cognitive function, and release of counterregulatory hormones in subjects with functional hypoglycaemia.

Nine patients with food-relieved hypoglycaemic symptoms, in whom insulinoma and other organic diseases presenting with hypoglycaemia had been ruled out, and nine matched controls, participated in the study. Subjects were studied during a 5-h controlled (Biostator) insulin-induced (1-2 mU kg-1 min-1) hypoglycaemic clamp. After 1 h of euglycaemia, we aimed to lower the glucose level in arterialized venous blood in a stepwise manner at 30-min intervals to 3.5, 3.0, and 2.0 mmol l-1, and to withhold these levels for a further 30 min. At euglycaemia and at the end of the latter steps, the visual reaction time and cognitive function (digit span, letter cancellation and trail making) were tested, together with recording symptoms and signs of hypoglycaemia. Counter-regulatory hormones were measured at 20-min intervals. In the patients, clinical signs and symptoms of hypoglycaemia developed at median blood glucose levels of 2.6-2.8 and 2.8-3.1 mmol l-1, respectively. By contrast, the blood glucose levels were 0.4-0.8 mmol l-1 lower in control subjects (P less than 0.05). Similarly, the median threshold for deterioration of visual reaction time was 2.8 mmol l-1 in patients and 2.1 mmol l-1 in controls (P less than 0.01). A similar trend was observed for the results of the neuropsychological tests. Visual reaction time deteriorated in all subjects, whereas the cognitive function of some of the subjects in each group remained unchanged during hypoglycaemia. The glycaemic thresholds for release of cortisol, glucagon and growth hormone were significantly higher in patients (P less than 0.05), whereas the thresholds for catecholamine release showed no significant difference from controls. Despite the comparable glucose infusion rates required to sustain each of the hypoglycaemic levels in the two groups, the control subjects achieved lower glucose levels, suggesting that there is resistance to insulin or glucose in functional hypoglycaemia. In conclusion, the present study suggests that the existence of a higher threshold for symptoms and signs, as well as for deterioration of brain function, may explain every-day hypoglycaemic symptoms, despite normal glucose levels, in subjects with functional hypoglycaemia. However, the hypothesis should be tested further using a blinded approach, including euglycaemic control studies.

Adult↗

PubMed1993

Cytochalasin modulation of nicotinic cholinergic receptor expression and muscarinic receptor function in human TE671/RD cells: a possible functional role of the cytoskeleton.

Previous studies have shown that cells of the TE671/RD human clonal line express muscle-type nicotinic acetylcholine receptors (nAChR) and m3-type muscarinic acetylcholine receptors (mAChR) whose numbers and function are regulated by agonist treatment and second messenger modulation. Here we show that cytochalasin treatment, which causes disruption of actin networks, induces marked changes in the numbers and distribution of nAChR, but not mAChR. Moreover, whereas cytochalasin treatment fails to alter nAChR function significantly, it acutely potentiates mAChR-mediated phosphoinositide hydrolysis. Treatment of TE671/RD cells with different cytochalasin analogues (rank order efficacy at 5 micrograms/ml is H > J = B = C = D > A = E) produces a two- to fourfold increase in numbers of membrane-bound nAChR (Bmax in units of specific 125I-labeled alpha-bungarotoxin binding per milligram of membrane protein). nAChR up-regulation is evident after 1-2 days of cytochalasin B exposure, is maximal after 3-6 days of drug treatment, and is dominated by an approximately 10-fold increase (per cell) in an intracellular nAChR pool. Cytochalasin-induced nAChR up-regulation is similar in magnitude to, but not additive with, up-regulation of nAChR following chronic exposure to nicotine or phorbol ester. Northern blot analysis shows a four- to five-fold coordinate increase in levels of mRNA that encode nAChR alpha, beta, gamma, or delta subunits in cytochalasin-treated cells, suggesting that nAChR up-regulation has a possible transcriptional basis. Studies done using a 86Rb+ efflux assay indicate that cytochalasin treatment has no significant effect on nAChR function. By contrast, cytochalasin treatment has no effect on the numbers of mAChR as assessed by binding studies with the radioantagonist 3H-labeled quinuclidinyl benzilate, but it induces marked enhancement of carbachol-stimulated, but not basal, phosphoinositide hydrolysis. These studies suggest that presumed modulation by cytochalasin treatment of cytoskeletal microfilament integrity can differentially influence expression and function of mAChR (a prototype of the metabotropic receptor superfamily) and nAChR (a prototype of the ligand-gated ion-channel superfamily). The results also suggest possible new roles for the cytoskeleton in regulation of membrane receptor expression, function, and cross talk.

Carbachol↗

PubMed1994

Nutrition and function: is there a relationship between body mass index and the functional capabilities of community-dwelling elderly?

OBJECTIVE: To determine if there is a relationship between body mass index and the ability to perform the usual activities of living in a sample of community-dwelling elderly. DESIGN: Secondary data analysis of The National Health and Nutrition Examination Survey-I Epidemiologic Follow-up Study (1982-1984). Follow-up home interview of a population-based sample originally interviewed between 1971 and 1975 in the National Health and Nutrition Examination Survey-I (NHANES-I). PARTICIPANTS: Survivors of the original NHANES-I cohort who were 65 years of age or older and who were living at home at the time of the second interview (n = 3061). Excluded were those who could not be found, refused participation, or were institutionalized (n = 220), and those without complete height and weight data (n = 194). MAIN OUTCOME MEASURE: Functional status as measured by a 26-item battery. RESULTS: Bivariate analysis revealed a greater risk for functional impairment for subjects with a low body mass index or a high body mass index. The greater the extreme of body mass index (either higher or lower), the greater the risk for functional impairment. Logistic regression analysis indicated that both high and low body mass index continued to be significantly related to functional status when 22 other potential confounders were included in the model. CONCLUSION: The body mass index is related to the functional capabilities of community-dwelling elderly. The inclusion of this simple measurement in the comprehensive assessment of community-dwelling elderly is supported.

Activities of Daily Living↗

PubMed1996

Retrograde migration of the site of functional block: a mechanism underlying resolution of functional retrograde bundle branch block during AV reentrant tachycardia.

INTRODUCTION: Functional bundle branch blocks during supraventricular tachycardia have been described, and their sustainment has been attributed to concealed conduction. Such blocks frequently resolve spontaneously, but the electrophysiologic mechanism of resolution has not been well described. This report describes the resolution of functional bundle branch block through proximal migration of the site of block. METHODS AND RESULTS: During electrophysiologic study of a patient with reentrant antidromic tachycardia via an atriofascicular accessory pathway, functional retrograde right bundle branch block could be readily induced following tachycardia initiation with right ventricular apical pacing. Resolution of this block was associated with shortening of the tachycardia cycle length. Electrogram recordings along the right bundle branch during tachycardia determined that resolution of the functional retrograde right bundle branch block was associated with migration of the site of block from the distal to the proximal right bundle. When the site of block was directly at the recording site, both anterograde and retrograde activation of the right bundle was demonstrated. CONCLUSION: Migration of the site of block is a mechanism of resolution for functional conduction blocks maintained by concealed conduction.

Adult↗

PubMedDate not supplied

Characterization of the point spread function and modulation transfer function of scattered radiation using a digital imaging system.

A digital radiographic system was used to measure the distribution of scattered x radiation from uniform slabs of Lucite at various thicknesses. Using collimation and air gap techniques, [primary + scatter] images and primary images were digitally acquired, and subtracted to obtain scatter images. The scatter distributions measured using small circular apertures were computer fit to an analytical function, representing the circular aperture function convolved with a modified Gaussian point spread function (PSF). On the basis of goodness of fit criterion, the proposed Gaussian function is a very good model for the scatter PSF. The measured scatter PSF's are reported for various Lucite thicknesses. Using the PSF's, the modulation transfer functions are calculated, and this spatial frequency information may have value in analytical scatter removal techniques, grid design, and air gap optimization.

Computers↗

PubMed1975

Bacteriophage P22 virion protein which performs an essential early function. II. Characterization of the gene 16 function.

P16 is a virion protein and, as such, is incorporated into the phage head as a step in morphogenesis. The role of P16 in assembly is not essential since particles are formed without this protein which appear normal by electron microscopy. P16 is essential when the particle infects a cell in the following cycle of infection. In the absence of functional P16, the infection does not appear to proceed beyond release of phage DNA from the capsid. No known genes are expressed, no DNA is transcribed, and the host cell survives the infection, continuing to grow and divide normally. The P16 function is required only during infection for the expression of phage functions. Induction in the absence of P16 proceeds with the expression of early and late genes and results in particle formation. P16 must be incorporated during morphogenesis into progeny particles after both infection and induction for the progeny to be infectious. The P16 function is necessary for transduction as well as for infection. Its activity is independent of new protein synthesis and it is not under immunity control. P16 can act in trans, but appears to act preferentially on the phage or phage DNA with which it is packaged. The data from complementation studies are compatible with P16 release from the capsid with the phage DNA. In the absence of P16 the infection is blocked, but the phage genome is not degraded. The various roles which have been ruled out for P16 are: (i) an early regulatory function, (ii) an enzymatic activity necessary for phage production, (iii) protection of phage DNA from host degradation enzymes, (iv) any generalized alteration of the host cell, (v) binding parental DNA to the replication complex, and (vi) any direct involvement in the replication of P22 DNA. P16 can be responsible for: (i) complete release of the DNA and disengagement from the capsid, (ii) bringing the released DNA to some necessary cell site or compartment such as the cytoplasm, (iii) removal of other virion proteins from the injected DNA, and (iv) alterations of the structure of the injected DNA.

Adsorption↗

PubMed1993

A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1-mediated pathway.

The PKC1 gene of Saccharomyces cerevisiae encodes a homolog of mammalian protein kinase C that is required for yeast cell growth. Loss of PKC1 function results in cell lysis due to an inability to remodel the cell wall properly during growth. The PKC1 gene has been proposed to regulate a bifurcated pathway, on one branch of which function four putative protein kinases that catalyze a linear cascade of protein phosphorylation culminating in the activation of the mitogen-activated protein kinase homolog, Mpk1p. Here we describe two genes whose overexpression suppress both an mpk1 delta mutation and a pkc1 delta mutation. One of these genes is identical to the previously identified PPZ2 gene. The PPZ2 gene is predicted to encode a type 1-related protein phosphatase and is functionally redundant with a closely related gene, designated PPZ1. Deletion of both PPZ1 and PPZ2 resulted in a temperature-dependent cell lysis defect similar to that observed for bck1 delta, mkk1,2 delta, or mpk1 delta mutants. However, ppz1,2 delta mpk1 delta triple mutants displayed a cell lysis defect at all temperatures. The additivity of the ppz1,2 delta defect with the mpk1 delta defect, combined with the results of genetic epistasis experiments, suggested either that the PPZ1- and PPZ2-encoded protein phosphatases function on a branch of the PKC1-mediated pathway different from that defined by the protein kinases or that they play an auxiliary role in the pathway. The other suppressor gene, designated BCK2 (for bypass of C kinase), is predicted to encode a 92-kDa protein that is rich in serine and threonine residues. Genetic interactions between BCK2 and other pathway components suggested that BCK2 functions on a common pathway branch with PPZ1 and PPZ2.

Amino Acid Sequence↗