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11.
ScaC, an adaptor protein carrying a novel cohesin that expands the dockerin-binding repertoire of the Ruminococcus flavefaciens 17 cellulosome 总被引:1,自引:0,他引:1
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Rincón MT Martin JC Aurilia V McCrae SI Rucklidge GJ Reid MD Bayer EA Lamed R Flint HJ 《Journal of bacteriology》2004,186(9):2576-2585
A new gene, designated scaC and encoding a protein carrying a single cohesin, was identified in the cellulolytic rumen anaerobe Ruminococcus flavefaciens 17 as part of a gene cluster that also codes for the cellulosome structural components ScaA and ScaB. Phylogenetic analysis showed that the sequence of the ScaC cohesin is distinct from the sequences of other cohesins, including the sequences of R. flavefaciens ScaA and ScaB. The scaC gene product also includes at its C terminus a dockerin module that closely resembles those found in R. flavefaciens enzymes that bind to the cohesins of the primary ScaA scaffoldin. The putative cohesin domain and the C-terminal dockerin module were cloned and overexpressed in Escherichia coli as His(6)-tagged products (ScaC-Coh and ScaC-Doc, respectively). Affinity probing of protein extracts of R. flavefaciens 17 separated in one-dimensional and two-dimensional gels with recombinant cohesins from ScaC and ScaA revealed that two distinct subsets of native proteins interact with ScaC-Coh and ScaA-Coh. Furthermore, ScaC-Coh failed to interact with the recombinant dockerin module from the enzyme EndB that is recognized by ScaA cohesins. On the other hand, ScaC-Doc was shown to interact specifically with the recombinant cohesin domain from ScaA, and the ScaA-Coh probe was shown to interact with a native 29-kDa protein spot identified as ScaC by matrix-assisted laser desorption ionization-time of flight mass spectrometry. These results suggest that ScaC plays the role of an adaptor scaffoldin that is bound to ScaA via the ScaC dockerin module, which, via the distinctive ScaC cohesin, expands the range of proteins that can bind to the ScaA-based enzyme complex. 相似文献
12.
KR Rupesh PL PremKumar Vasanth V Shiva Kumar Seetharaman S Jayachandran 《BMC microbiology》2002,2(1):5-7
Background
Seeds of the legume plant Lathyrus sativus, which is grown in arid and semi arid tropical regions, contain Diamino Propionic acid (DAP). DAP is a neurotoxin, which, when consumed, causes a disease called Lathyrism. Lathryrism may manifest as Neurolathyrism or Osteolathyrism, in which the nervous system, and bone formation respectively, are affected. DAP ammonia lyase is produced by a few microorganisms such as Salmonella typhi, Salmonella typhimurium and Pseudomonas, and is capable of detoxifying DAP. 相似文献13.
The pattern of polypeptides specifically secreted by cells after infection with vaccinia virus has been analyzed. A complex pattern of apparently virus-specified polypeptides exhibiting temporal control of the type seen with intracellular polypeptides after virus infection was observed. Some of the specifically secreted polypeptides were shown to be modified by glycosylation and sulfation. The possible significance of these results is discussed. 相似文献
14.
15.
16.
17.
Siying Wang Wen-Mei Yu Wanming Zhang Keith R. McCrae Benjamin G. Neel Cheng-Kui Qu 《The Journal of biological chemistry》2009,284(2):913-920
Mutations in SHP-2 phosphatase (PTPN11) that cause hyperactivation
of its catalytic activity have been identified in Noonan syndrome and various
childhood leukemias. Recent studies suggest that the gain-of-function (GOF)
mutations of SHP-2 play a causal role in the pathogenesis of these diseases.
However, the molecular mechanisms by which GOF mutations of SHP-2 induce these
phenotypes are not fully understood. Here, we show that GOF mutations in
SHP-2, such as E76K and D61G, drastically increase spreading and migration of
various cell types, including hematopoietic cells, endothelial cells, and
fibroblasts. More importantly, in vivo angiogenesis in SHP-2 D61G
knock-in mice is also enhanced. Mechanistic studies suggest that the increased
cell migration is attributed to the enhanced β1 integrin outside-in
signaling. In response to β1 integrin cross-linking or fibronectin
stimulation, activation of ERK and Akt kinases is greatly increased by SHP-2
GOF mutations. Also, integrin-induced activation of RhoA and Rac1 GTPases is
elevated. Interestingly, mutant cells with the SHP-2 GOF mutation (D61G) are
more sensitive than wild-type cells to the suppression of cell motility by
inhibition of these pathways. Collectively, these studies reaffirm the
positive role of SHP-2 phosphatase in cell motility and suggest a new
mechanism by which SHP-2 GOF mutations contribute to diseases.SHP-2, a multifunctional SH2 domain-containing protein-tyrosine phosphatase
implicated in diverse cell signaling processes
(1–3),
plays a critical role in cellular function. Homozygous deletion of Exon
2 (4) or Exon 3
(5) of the SHP-2 gene
(PTPN11) in mice leads to early embryonic lethality prior to and at
midgestation, respectively. SHP-2 null mutant mice die much earlier, at
peri-implantation (4). Exon
3 deletion mutation of SHP-2 blocks hematopoietic potential of embryonic
stem cells both in vitro and in vivo
(6–8),
whereas SHP-2 null mutation causes inner cell mass death and diminished
trophoblast stem cell survival
(4). Recent studies on SHP-2
conditional knock-out or tissue-specific knock-out mice have further revealed
an array of important functions of this phosphatase in various physiological
processes
(9–12).
The phenotypes demonstrated by loss of SHP-2 function are apparently
attributed to the role of SHP-2 in the cell signaling pathways induced by
growth factors/cytokines. SHP-2 generally promotes signal transmission in
growth factor/cytokine signaling in both catalytic-dependent and -independent
fashion
(1–3).
The positive role of SHP-2 in the intracellular signaling processes, in
particular, the ERK3
and PI3K/Akt kinase pathways, has been well established, although the
underlying mechanism remains elusive, in particular, the signaling function of
the catalytic activity of SHP-2 in these pathways is poorly understood.In addition to the role of SHP-2 in cell proliferation and differentiation,
the phenotypes induced by loss of SHP-2 function may be associated with its
role in cell migration. Indeed, dominant negative SHP-2 disrupts
Xenopus gastrulation, causing tail truncations
(13,
14). Targeted Exon 3
deletion mutation in SHP-2 results in decreased cell spreading, migration
(15,
16), and impaired limb
development in the chimeric mice
(7). The role of SHP-2 in cell
adhesion and migration has also been demonstrated by catalytically inactive
mutant SHP-2-overexpressing cells
(17–20).
The molecular mechanisms by which SHP-2 regulates these cellular processes,
however, have not been well defined. For example, the role of SHP-2 in the
activation of the Rho family small GTPases that is critical for cell motility
is still controversial. Both positive
(19,
21,
22) and negative roles
(18,
23) for SHP-2 in this context
have been reported. Part of the reason for this discrepancy might be due to
the difference in the cell models used. Catalytically inactive mutant SHP-2
was often used to determine the role of SHP-2 in cell signaling. In the
catalytically inactive mutant SHP-2-overexpressing cells, the catalytic
activity of endogenous SHP-2 is inhibited. However, as SHP-2 also functions
independent of its catalytic activity, overexpression of catalytically
deficient SHP-2 may also increase its scaffolding function, generating complex
effects.The critical role of SHP-2 in cellular function is further underscored by
the identification of SHP-2 mutations in human diseases. Genetic lesions in
PTPN11 that cause hyperactivation of SHP-2 catalytic activity have
been identified in the developmental disorder Noonan syndrome
(24) and various childhood
leukemias, including juvenile myelomonocytic leukemia (JMML), B cell acute
lymphoblastic leukemia, and acute myeloid leukemia
(25,
26). In addition, activating
mutations in SHP-2 have been identified in sporadic solid tumors
(27). The SHP-2 mutations
appear to play a causal role in the development of these diseases as SHP-2
mutations and other JMML-associated Ras or Neurofibromatosis 1 mutations are
mutually exclusive in the patients
(24–27).
Moreover, single SHP-2 gain-of-function (GOF) mutations are sufficient to
induce Noonan syndrome, cytokine hypersensitivity in hematopoietic progenitor
cells, and JMML-like myeloproliferative disease in mice
(28–32).
Gain-of-function cell models derived from the newly available SHP-2 GOF
mutation (D61G) knock-in mice
(28) now provide us with a
good opportunity to clarify the role of SHP-2 in cell motility. Unlike the
dominant negative approach in which overexpression of mutant forms of SHP-2
generates complex effects, the SHP-2 D61G knock-in model eliminates this
possibility as the mutant SHP-2 is expressed at the physiological level
(28). Additionally, defining
signaling functions of GOF mutant SHP-2 in cell movement can also help
elucidate the molecular mechanisms by which SHP-2 mutations contribute to the
relevant diseases. 相似文献
18.
A mathematical model is proposed which systematically investigates complex calcium oscillations in pancreatic acinar cells. This model is based on calcium-induced calcium release via inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR) and includes calcium modulation of inositol (1,4,5) trisphosphate (IP3) levels through feedback regulation of degradation and production. In our model, the apical and the basal regions are separated by a region containing mitochondria, which is capable of restricting Ca2+ responses to the apical region. We were able to reproduce the observed oscillatory patterns, from baseline spikes to sinusoidal oscillations. The model predicts that calcium-dependent production and degradation of IP3 is a key mechanism for complex calcium oscillations in pancreatic acinar cells. A partial bifurcation analysis is performed which explores the dynamic behaviour of the model in both apical and basal regions. 相似文献
19.
20.
William R. McCrae 《BMJ (Clinical research ed.)》1935,1(3872):621-622