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Biomedical subjects

C S Shi

Publications and source records attributed to C S Shi.

At least 19 recordsLinked to original sources
PubMed2001

PYK2 links G(q)alpha and G(13)alpha signaling to NF-kappa B activation.

Signaling via a variety of G-protein-coupled receptors (GPCRs) leads to activation of nuclear factor (NF)-kappa B. Evidence exists for a signaling pathway initiated by the B2 type bradykinin receptor via G(q) activation, which leads to the sequential stimulation of phosphoinositide 3-kinase (PI3K), the serine/threonine kinase Akt, I kappa B kinases, and finally nuclear factor NF-kappa B-dependent transcription. GPCR-mediated G(q)alpha or G(13)alpha activation also potently stimulates the tyrosine kinase PYK2. In this study we tested whether G(q)alpha- and/or G(13)alpha-induced PYK2 activation contributes to GPCR-mediated NF-kappa B activation. Among the GTPase-deficient forms of G alpha tested, G(13)alpha and G(q)alpha most potently stimulated an NF-kappa B-dependent reporter gene. PYK2 activated the same reporter gene and synergized with either G(q)alpha Q209L (QL) or G(13)alpha Q226L (QL). Placing PYK2 upstream of both PI3K and Akt activation, PYK2 activated Akt through a PI3K-dependent pathway, and either a dominant negative form of Akt or the PI3K inhibitor LY294002 blocked PYK2-stimulated NF-kappa B-dependent transcription. Placing PYK2 downstream of G-protein activation, a kinase-dead form of PYK2, PYK2 (KD), blocked NF-kappa B-dependent transcription triggered by signaling through the muscarinic receptor type 1 and either G(q)alpha QL or G(13)alpha QL. PYK2 (KD) also blocked Akt activation by the same stimuli. These results indicate that PYK2 can link G-protein activation through PI3K, Akt, and I kappa B kinase to NF-kappa B activation.

Chromones↗
PubMed2001

Regulator of G-protein signaling 3 (RGS3) inhibits Gbeta1gamma 2-induced inositol phosphate production, mitogen-activated protein kinase activation, and Akt activation.

Regulator of G-protein signaling 3 (RGS3) enhances the intrinsic rate at which Galpha(i) and Galpha(q) hydrolyze GTP to GDP, thereby limiting the duration in which GTP-Galpha(i) and GTP-Galpha(q) can activate effectors. Since GDP-Galpha subunits rapidly combine with free Gbetagamma subunits to reform inactive heterotrimeric G-proteins, RGS3 and other RGS proteins may also reduce the amount of Gbetagamma subunits available for effector interactions. Although RGS6, RGS7, and RGS11 bind Gbeta(5) in the absence of a Ggamma subunit, RGS proteins are not known to directly influence Gbetagamma signaling. Here we show that RGS3 binds Gbeta(1)gamma(2) subunits and limits their ability to trigger the production of inositol phosphates and the activation of Akt and mitogen-activated protein kinase. Co-expression of RGS3 with Gbeta(1)gamma(2) inhibits Gbeta(1)gamma(2)-induced inositol phosphate production and Akt activation in COS-7 cells and mitogen-activated protein kinase activation in HEK 293 cells. The inhibition of Gbeta(1)gamma(2) signaling does not require an intact RGS domain but depends upon two regions in RGS3 located between acids 313 and 390 and between 391 and 458. Several other RGS proteins do not affect Gbeta(1)gamma(2) signaling in these assays. Consistent with the in vivo results, RGS3 inhibits Gbetagamma-mediated activation of phospholipase Cbeta in vitro. Thus, RGS3 may limit Gbetagamma signaling not only by virtue of its GTPase-activating protein activity for Galpha subunits, but also by directly interfering with the activation of effectors.

Animals↗
PubMed2000

G13alpha-mediated PYK2 activation. PYK2 is a mediator of G13alpha -induced serum response element-dependent transcription.

G(12)alpha/G(13)alpha transduces signals from G-protein-coupled receptors to stimulate growth-promoting pathways and the early response gene c-fos. Within the c-fos promoter lies a key regulatory site, the serum response element (SRE). Here we show a critical role for the tyrosine kinase PYK2 in muscarinic receptor type 1 and G(12)alpha/G(13)alpha signaling to an SRE reporter gene. A kinase-inactivate form of PYK2 (PYK2 KD) inhibits muscarinic receptor type 1 signaling to the SRE and PYK2 itself triggers SRE reporter gene activation through a RhoA-dependent pathway. Placing PYK2 downstream of G-protein activation but upstream of RhoA, the expression of PYK2 KD blocks the activation of an SRE reporter gene by GTPase-deficient forms of G(12)alpha or G(13)alpha but not by RhoA. The GTPase-deficient form of G(13)alpha triggers PYK2 kinase activity and PYK2 tyrosine phosphorylation, and co-expression of the RGS domain of p115 RhoGEF inhibits both responses. Finally, we show that in vivo G(13)alpha, although not G(12)alpha, readily associates with PYK2. Thus, G-protein-coupled receptors via G(13)alpha activation can use PYK2 to link to SRE-dependent gene expression.

Amino Acid Substitution↗
PubMed2000

Regulator of G protein signaling 1 (RGS1) markedly impairs Gi alpha signaling responses of B lymphocytes.

Regulator of G protein signaling (RGS) proteins modulate signaling through pathways that use heterotrimeric G proteins as transducing elements. RGS1 is expressed at high levels in certain B cell lines and can be induced in normal B cells by treatment with TNF-alpha. To determine the signaling pathways that RGS1 may regulate, we examined the specificity of RGS1 for various G alpha subunits and assessed its effect on chemokine signaling. G protein binding and GTPase assays revealed that RGS1 is a Gi alpha and Gq alpha GTPase-activating protein and a potential G12 alpha effector antagonist. Functional studies demonstrated that RGS1 impairs platelet activating factor-mediated increases in intracellular Ca+2, stromal-derived factor-1-induced cell migration, and the induction of downstream signaling by a constitutively active form of G12 alpha. Furthermore, germinal center B lymphocytes, which are refractory to stromal-derived factor-1-triggered migration, express high levels of RGS1. These results indicate that RGS proteins can profoundly effect the directed migration of lymphoid cells.

Animals↗
PubMed2000

Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation.

STE20-related kinases play significant regulatory roles in a range of cellular responses to environmental stimuli. GCKR (also referred to as KHS1) is a serine/threonine protein kinase that has an STE20-like protein kinase domain and that stimulates the stress-activated protein kinase (SAPK, also referred to as Jun kinase or JNK) pathway. GCKR has a large C-terminal regulatory domain that provides sites for interactions with other proteins. Adaptor proteins mediate the interactions between signaling molecules. In this study we showed that the adaptor proteins Crk and CrkL associated with GCKR. When Crk-I, Crk-II, or CrkL was transiently expressed in HEK 293T cells along with GCKR, each coimmunoprecipitated with GCKR. Furthermore, in the Bcr-Abl transformed cell line, K562 endogenous GCKR and CrkL coimmunoprecipitated, indicating a constitutive association. Detection of the CrkL-GCKR interaction required the SH3 domains of CrkL and 2 regions in GCKR-1 between amino acids 387 and 395 that contains a consensus SH3 binding motif and the other between amino acids 599 and 696. Crk or CrkL overexpression increased GCKR catalytic activity. A dominant negative form of Ras abolished Crk- or CrkL-induced GCKR activation, suggesting a dependence on Ras activation for their activation of GCKR. Finally, we showed impairment of the known ability of CrkL to activate the SAPK pathway by a catalytically inactive form of GCKR or by a GCKR antisense construct. Thus, GCKR associates with other proteins through interactions mediated by SH2/SH3 adaptor proteins, which can lead to GCKR and SAPK activation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

RGS3 is a GTPase-activating protein for g(ialpha) and g(qalpha) and a potent inhibitor of signaling by GTPase-deficient forms of g(qalpha) and g(11alpha).

Many Regulators of G protein Signaling (RGS) proteins accelerate the intrinsic GTPase activity of G(ialpha) and G(qalpha)-subunits [i.e., behave as GTPase-activating proteins (GAPs)] and several act as G(qalpha)-effector antagonists. RGS3, a structurally distinct RGS member with a unique N-terminal domain and a C-terminal RGS domain, and an N-terminally truncated version of RGS3 (RGS3CT) both stimulated the GTPase activity of G(ialpha) (except G(zalpha)) and G(qalpha) but not that of G(salpha) or G(12alpha). RGS3 and RGS3CT had G(qalpha) GAP activity similar to that of RGS4. RGS3 impaired signaling through G(q)-linked receptors, although RGS3CT invariably inhibited better than did full-length RGS3. RGS3 potently inhibited G(qalpha)Q209L- and G(11alpha)Q209L-mediated activation of a cAMP-response element-binding protein reporter gene and G(qalpha)Q209L induced inositol phosphate production, suggesting that RGS3 efficiently blocks G(qalpha) from activating its downstream effector phospholipase C-beta. Whereas RGS2 and to a lesser extent RGS10 also inhibited signaling by these GTPase-deficient G proteins, other RGS proteins including RGS4 did not. Mutation of residues in RGS3 similar to those required for RGS4 G(ialpha) GAP activity, as well as several residues N terminal to its RGS domain impaired RGS3 function. A greater percentage of RGS3CT localized at the cell membrane than the full-length version, potentially explaining why RGS3CT blocked signaling better than did full-length RGS3. Thus, RGS3 can impair Gi- (but not Gz-) and Gq-mediated signaling in hematopoietic and other cell types by acting as a GAP for G(ialpha) and G(qalpha) subfamily members and as a potent G(qalpha) subfamily effector antagonist.

Cells, Cultured↗
PubMed1999

TNF-mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related.

TNF-induced activation of stress activated protein kinases (SAPKs, Jun NH2-terminal kinases) requires TNF receptor associated factor 2 (TRAF2). TRAF2 is a potent activator of a 95-kDa serine/threonine kinase termed germinal center kinase related (GCKR, also referred to as KHS1), which signals activation of the SAPK pathway. Consistent with a role for GCKR in TNF- induced SAPK activation, a kinase-inactive mutant of GCKR is a dominant negative inhibitor of TRAF2-induced SAPK activation. Here we show that TRAF2 interacts with GCKR. This interaction depended upon the TRAF domain of TRAF2 and the C-terminal 150 aa of GCKR. The full activation of GCKR by TRAF2 required the TRAF2 RING finger domain. TNF treatment of a T cell line, Jurkat, increased both GCRK and SAPK activity and enhanced the coimmunoprecipitation of GCKR with TRAF2. Similar results were found with the B cell line HS-Sultan. These findings are consistent with a model whereby TNF signaling results in the recruitment and activation of GCKR by TRAF2, which leads to SAPK activation.

Amino Acid Sequence↗
PubMed1999

GCKR links the Bcr-Abl oncogene and Ras to the stress-activated protein kinase pathway.

The Bcr-Abl oncogene, found in Philadelphia chromosome-positive myelogenous leukemia (CML), activates Ras and triggers the stress-activated protein kinase (SAPK or Jun NH2-terminal kinase [JNK]) pathway. Interruption of Ras or SAPK activation dramatically reduces Bcr-Abl-mediated transformation. Here, we report that Bcr-Abl through a Ras-dependent pathway signals the serine/threonine protein kinase GCKR (Germinal Center Kinase Related) leading to SAPK activation. Either an oncogenic form of Ras or Bcr-Abl enhances GCKR catalytic activity and its activation of SAPK, whereas inhibition of GCKR impairs Bcr-Abl-induced SAPK activation. Bcr-Abl mutants that are impaired for GCKR activation are also unable to activate SAPK. Consistent with GCKR being a functional target in CML, GCKR is constitutively active in CML cell lines and found in association with Bcr-Abl. Our results indicate that GCKR is a downstream target of Bcr-Abl and strongly implicate GCKR as a mediator of Bcr-Abl in its transformation of cells.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Activation of stress-activated protein kinase/c-Jun N-terminal kinase, but not NF-kappaB, by the tumor necrosis factor (TNF) receptor 1 through a TNF receptor-associated factor 2- and germinal center kinase related-dependent pathway.

A key step by which tumor necrosis factor (TNF) signals the activation of nuclear factor-kappaB (NF-kappaB) and the stress-activated protein kinase (SAPK, also called c-Jun N-terminal kinase or JNK) is the recruitment to the TNF receptor of TNF receptor-associated factor 2 (TRAF2). However, the subsequent steps in TRAF2-induced SAPK and NF-kappaB activation remain unresolved. Here we report the identification of a TNF-responsive serine/threonine protein kinase termed GCK related (GCKR) that likely signals via mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase kinase 1 (MEKK1) to activate the SAPK pathway. TNF, TRAF2, and ultraviolet (UV) light, which in part uses the TNF receptor signaling pathway, all increased GCKR activity. A TRAF2 mutant, which inhibits both TRAF2-induced NF-kappaB and SAPK activation, blocked TNF-induced GCKR activation. Finally, interference with GCKR expression impeded TRAF2- and TNF-induced SAPK activation but not that of NF-kappaB. This suggests a divergence in the TNF signaling pathway that leads to SAPK and NF-kappaB activation, which is located downstream of TRAF2 but upstream of GCKR.

Amino Acid Sequence↗
PubMed1995

Extracting direction and curvature features of jaw movement traces with chain code.

Frontal chewing patterns have been classified in a manual and visual way on recorded movement tracks. The main aim of this study was to use a chain code method to extract the direction and curvature features of the tracks in the frontal plane. The test results indicate that the chain code can stand for the direction and curvature. The chewing movement tracks in the frontal plane can be clustered into chain code values. The method therefore appears to be useful in the classification of chewing movements.

Humans↗
PubMed1995

Prevalence of primary Sjögren's syndrome in China.

OBJECTIVE: To determine the prevalence rate of primary Sjögren's syndrome (SS) in a community population of 2066 adults in a Beijing suburban village, and 100 inpatients, who were not necessarily admitted for rheumatic diseases. METHODS: Questionnaire and serological studies of antinuclear antibodies, rheumatoid factor, and anti-SSA, anti-SSB antibodies were done. Possible positive subjects were given eye and oral examinations for objective evidence of xerostomia and keratoconjunctivitis sicca. RESULTS: According to the Copenhagen criteria, the prevalence rate of primary Sjögren's syndrome in China was 0.77%, and it was 0.33% by modified San Diego criteria. In 100 inpatients, we found 4 cases of primary Sjögren's syndrome by Copenhagen criteria, and one case by modified San Diego criteria. CONCLUSION: Primary Sjögren's syndrome is not a rare disease in China, but most cases are overlooked or misdiagnosed.

Adolescent↗
PubMed1994

Correlation between autoregressive moving-average model parameters of electromyogram of human jaw closing muscles and maximum clenching time at intercuspal position.

During maximum clenching in the intercuspal position, surface electromyograms of left masseter and anterior temporal muscles were sampled in 16 healthy subjects with natural dentitions to establish a four-order, autoregressive (AR) moving-average (MA) model of the myoelectrical signals. The correlation coefficients and the linear regression between the model parameters and the clenching time were calculated. The model parameters had the positive or the negative correlation, and AR model parameters had the higher correlation than MA model parameters. The model parameters relate to muscular fatigue and the slope of the regressive equation relates to the endurance time of the isometric contraction.

Adult↗
PubMed1994

Rheumatic diseases in China: ILAR-China study comparing the prevalence of rheumatic symptoms in northern and southern rural populations.

OBJECTIVE: To determine the prevalence of rheumatic diseases in Han Chinese in north and south China. METHODS: Samples of 4192 adults in the Beijing (north) and 5057 in the Shantou (south) areas, based on village administration registers, were studied. The same questionnaire was administered by doctors who then examined those with rheumatic symptoms. One observer (QYZ) took part in both studies. RESULTS: The prevalence of definite rheumatoid arthritis (RA) was 0.34% (95% CI; 0.20-0.51) in the north and 0.32% (0.16-0.47) in the south. Ankylosing spondylitis (AS) was noted in 0.26% of both samples (95% CI; 0.11-0.42 north and 0.14-0.40 south). Only 3 cases of systemic lupus erythematosus (SLE) in the north and one in the south were identified. General rheumatic pain was reported more frequently in the north. Lumbar problems were recorded on examination 5 times more frequently in the north than in the south [men, 25%:5.3%; women 38%:6.5%] and knee problems 10 times more frequently [men, 24%:1.8%; women, 36%:3.4%] in the north. The difference was greatest in the 55 to 64 year age group. CONCLUSION: The prevalence of RA was similar to that in other rural populations and Japan, but only half that reported from other industrialized communities. The prevalence of AS was similar to that in most Caucasian populations. SLE was too infrequent to establish a prevalence with confidence, but did not differ from that in other populations. A study is planned in the south to assess the contribution of interobserver error and/or differences in cultural response to the north/south differences observed in the prevalence of general rheumatic symptoms and back pain.

Adult↗
PubMed1993

Relationship between mean power frequency and potential of human masticatory muscles at rest position and clenching.

The EMG signals from left and right masseter and anterior temporal muscles of 40 healthy subjects were sampled at rest position and through gradually increased clench level to maximum voluntary contraction (MVC) at intercuspal position. A visual sense feedback of masseter muscle potential value was used for the subject to control clench level. The relationship between mean power frequency (MPF) and potential of EMG was investigated by a curvilinear regression of the second order. It was found that the relationship was of the second order logarithmic curve with maximum value of MPF. With the raising of the potential levels of EMG, the MPF increased at the lower clench levels and decreased at higher clench levels. The results indicate that controlling an identical clench level is necessary for using MPF to describe the functional state of masticatory muscles in the clinical situation.

Adult↗
PubMed1993

Elementary identification of a gnathosonic classification using an autoregressive model.

This was an investigation to determine the feasibility of an autoregressive (AR) model for establishing characteristic parameters from recorded occlusal sounds and develop their classification. Thirty four normal subjects with intact natural dentitions were selected for the study. The subjects' occlusal sounds from both sides of their faces respectively were sampled, and the gnathosonic classification (Class A, B and C) was established by observing the original recorded wave pattern and measuring the duration. Then, a 20 order AR model was calculated with the collected data, and the AR model coefficients were found to be similar to the indices of Bayes' discriminatory analysis. The total conformation rates of the modelled left and right occlusal sounds to the classification, estimated by Bayes' discriminant functions were 97.06% and 88.24% respectively. AR coefficients representing the characteristics of human occlusal sounds can be helpful in their classification and allow computer diagnosis of occlusal disorders.

Acoustics↗
PubMed1992

Correlations between an autoregressive model coefficient of the electromyogram of human jaw-closing muscles and maximum clenching time at the intercuspal position.

During maximum clenching in the intercuspal position, surface electromyograms of both masseters and both anterior temporales in seven healthy subjects with intact natural dentitions were sampled to generate a four-order, autoregressive model of the myoelectrical signal. The correlation coefficients and the linear regression between the model coefficients and the clenching time were calculated. The first-order autoregressive coefficient had the greatest negative correlation on average. In this model the first-order coefficient relates to muscular fatigue and the slope of the regressive equation relates to the length of time the isometric contraction can be maintained.

Adult↗
PubMed1992

Discrimination of clenches at varied jaw positions using autoregressive model coefficients of myoelectrical activities of anterior temporal and masseter muscles.

During 10% maximum clenching at intercuspal, protruded, retruded contact and lateral positions, the surface electromyograms (EMG) of bilateral anterior temporal and masseter muscles of 20 normal subjects with intact natural dentitions were recorded. The autoregressive (AR) model of the sampled EMG was then built and the obtained coefficients of the AR model were accepted as featured parameters of the EMG. Finally Bayes' stepwise discriminant analysis was used for establishing discriminant functions of estimating low level clenches at varied jaw positions. It was found that total conformation rates of internal and external sample substitution (15 and 5 subjects) were 82.67% and 78% respectively; the discriminant effect between intercuspal and retruded contact position was not up to predicted standard. The results indicate that AR model coefficients may describe the characteristics of surface EMG of masticatory muscles and easily be used in multiple statistical analysis, from which the classification and diagnosis may be taken.

Adult↗