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1.
The excitation lifetimes of photosynthetic pigments and the times needed for energy transfer between pigments in various algae, were determined in vitro and in vivo. For this purpose, the time curves of fluorescence rise and decay were measured by means of Brody''s instrument (10), and compared with theoretical curves obtained by the method of “convolution of the first kind.”1 相似文献
2.
《The Western journal of medicine》1961,95(6):409-410
After several years of favorable experience with registered nurses giving intravenous injections of fluids under the criteria set out in a joint statement by the California Medical Association, the California Hospital Association and the California Nurses'' Association,* it was proposed that it would be appropriate for registered nurses to administer blood. Careful study of current experience in various places with registered nurses giving blood transfusions convinced a joint committee that it recommend the adoption of the following statement which was approved by the associations indicated. 相似文献
3.
A variety of diagnostic advances including radioimmunoassay of adrenocorticotropic hormone (ACTH) have increased the number of methods for laboratory investigation of Cushing syndrome.* However, experience with these procedures has led to a recognition of their limitations. We have developed an algorithm which incorporates these newer techniques and minimizes the number of procedures required to diagnose the various causes of Cushing syndrome. At present, we recommend pituitary surgical operations for pituitary-dependent Cushing syndrome because we believe this disease is caused by the development of a pituitary ACTH-secreting tumor. 相似文献
4.
Since 1957 we have treated more than 429 patients who had pituitary neoplasms, most of which were hormone-secreting tumors. Long-term follow-up in the large group of patients treated for acromegaly shows a median survival of better than 16 years, with improvement over time. The short-term follow-up results in patients with Cushing* disease, Nelson syndrome and chromophobe adenoma are very encouraging. To compare these excellent results with those following surgical procedures, a large study of patients followed for a long period after the operations is needed. 相似文献
5.
Tyrone M. Reyes 《The Western journal of medicine》1991,154(5):632-633
The international community has perspective and experience that will freshen our approaches to rehabilitation. Martin Grabois, MD*, editor of this special section, has gathered articles written by experts from other countries. The intention is to stimulate thought, discussion, and action—and to broaden horizons. 相似文献
6.
Oceanic islands are renowned for the profound scientific insights that their fascinating biotas have provided to biologists during the past two centuries. Research presented at Island Biology 2014—an international conference, held in Honolulu, Hawaii (7–11 July 2014), which attracted 253 presenters and 430 participants from at least 35 countries1—demonstrated that islands are reclaiming a leading role in ecology and evolution, especially for synthetic studies at the intersections of macroecology, evolution, community ecology and applied ecology. New dynamics in island biology are stimulated by four major developments. We are experiencing the emergence of a truly global and comprehensive island research community incorporating previously neglected islands and taxa. Macroecology and big-data analyses yield a wealth of global-scale synthetic studies and detailed multi-island comparisons, while other modern research approaches such as genomics, phylogenetic and functional ecology, and palaeoecology, are also dispersing to islands. And, increasingly tight collaborations between basic research and conservation management make islands places where new conservation solutions for the twenty-first century are being tested. Islands are home to a disproportionate share of the world''s rare (and extinct) species, and there is an urgent need to develop increasingly collaborative and innovative research to address their conservation requirements. 相似文献
7.
Kelly D. Sullivan Akihisa Nakagawa Ding Xue Joaquín M Espinosa 《Cell cycle (Georgetown, Tex.)》2015,14(12):1771-1778
Activation of caspases is an integral part of the apoptotic cell death program. Collectively, these proteases target hundreds of substrates, leading to the hypothesis that apoptosis is “death by a thousand cuts”. Recent work, however, has demonstrated that caspase cleavage of only a subset of these substrates directs apoptosis in the cell. One such example is C. elegans CNT-1, which is cleaved by CED-3 to generate a truncated form, tCNT-1, that acquires a potent phosphoinositide-binding activity and translocates to the plasma membrane where it inactivates AKT survival signaling. We report here that ACAP2, a homolog of C. elegans CNT-1, has a pro-apoptotic function and an identical phosphoinositide-binding pattern to that of tCNT-1, despite not being an apparent target of caspase cleavage. We show that knockdown of ACAP2 blocks apoptosis in cancer cells in response to the chemotherapeutic antimetabolite 5-fluorouracil and that ACAP2 expression is down-regulated in some esophageal cancers, leukemias and lymphomas. These results suggest that ACAP2 is a functional homolog of C. elegans CNT-1 and its inactivation or downregulation in human cells may contribute to cancer development.The caspases (cysteine aspartic acid proteases) are a class of proteases with diverse roles in cellular physiology including differentiation, inflammation and cell death.1–3 Caspases play a critical role in apoptosis, where they collectively target hundreds of proteins. One prevailing view is that caspases drive apoptosis through a mass action effect due to hundreds of proteolytic cleavage events that lead to cellular disassembly and cell death.4 Recent studies, however, suggest that proteolysis of most substrates may simply be a bystander effect and that caspase cleavage of key proteins controlling a few specific cellular processes is what functionally drives apoptosis.5 Although much of the work to date has focused on factors acting upstream of caspase activation, it is becoming increasingly clear that events downstream of this commitment step are also tightly regulated and critically important for apoptosis. Presently, there is evidence of requirements for caspase-mediated control of the BCL2 family of anti-apoptotic proteins, mitochondrial elimination, chromosome fragmentation, phosphatidylserine externalization, and, as we have recently reported, inactivation of the AKT survival signaling pathway in programmed cell death (6-10 Therefore, a more thorough understanding of physiologically relevant caspase targets will increase our understanding of apoptosis in the context of animal development and disease.
Open in a separate window*Roles of DRP1 and FIS1 in apoptosis related mitochondrial elimination have not been extensively tested.#Proteins have similar functions but are not homologous 相似文献
Table 1
Human homologues of functional caspase targets in C. elegans. A summary of identified caspase substrates and caspase downstream events important for cell death execution in C. elegans and humansFunctional Caspase Targets | ||
---|---|---|
C. elegans | Human | Downstream Events |
CED-9 | BCL2 | Inactivation of apoptosis inhibitors |
DRP-1 | DRP1a | Mitochondrial elimination |
DCR-1 | DFF40/45# | Chromosome fragmentation |
CED-8 | XKR8 | PS externalization |
CNT-1 | ACAP2 | Inactivation of AKT signaling |
8.
An antibiotic resistant staphylococcus with bacteriophage pattern 52/42B/80/81* is frequently responsible for infectious outbreaks in the newborn nursery. Some time after an outbreak had occurred in the University of California''s hospital nursery, family members of the infants were found to be infected with this strain. Two families were studied in detail. In one of them, infection developed in six of the seven members within eight months after the infant''s arrival. In the other, half of the family members had recurrent infections during a 13-month period.Infants who left the nursery as asymptomatic carriers were found as likely to transmit the infectious strain as those with clinical infection. Considerable time sometimes elapsed before infection developed in either the infant or the family members. In one instance the first familial infection occurred six months after the infant had left the nursery as an asymptomatic carrier.Newborn infants are quite likely to disseminate antibiotic resistant staphylococci which they may acquire from a hospital nursery. Infections developing among persons in contact with a young infant must be treated with the possibility of a resistant hospital staphylococcus in mind. 相似文献
9.
Aaron C. Mason Stuart J. Haring John M. Pryor Cathy A. Staloch Tze Fei Gan Marc S. Wold 《The Journal of biological chemistry》2009,284(8):5324-5331
Replication protein A (RPA), the eukaryotic single-stranded DNA-binding
complex, is essential for multiple processes in cellular DNA metabolism. The
“canonical” RPA is composed of three subunits (RPA1, RPA2, and
RPA3); however, there is a human homolog to the RPA2 subunit, called RPA4,
that can substitute for RPA2 in complex formation. We demonstrate that the
resulting “alternative” RPA (aRPA) complex has solution and DNA
binding properties indistinguishable from the canonical RPA complex; however,
aRPA is unable to support DNA replication and inhibits canonical RPA function.
Two regions of RPA4, the putative L34 loop and the C terminus, are responsible
for inhibiting SV40 DNA replication. Given that aRPA inhibits canonical RPA
function in vitro and is found in nonproliferative tissues, these
studies indicate that RPA4 expression may prevent cellular proliferation via
replication inhibition while playing a role in maintaining the viability of
quiescent cells.Replication protein A
(RPA)3 is a stable
complex composed of three subunits (RPA1, RPA2, and RPA3) that binds
single-stranded DNA (ssDNA) nonspecifically. RPA (also referred to as
canonical RPA) is essential for cell viability
(1), and viable missense
mutations in RPA subunits can lead to defects in DNA repair pathways or show
increased chromosome instability. For example, a missense change in a high
affinity DNA-binding domain (DBD) was demonstrated to cause a high rate of
chromosome rearrangement and lymphoid tumor development in heterozygous mice
(2). RPA has also been shown to
have increased expression in colon and breast cancers
(3,
4). High RPA1 and RPA2 levels
in cancer cells are also correlated with poor overall survival
(3,
4), which is consistent with
RPA having a role in efficient cell proliferation.RPA is a highly conserved complex as all eukaryotes contain homologs of
each of the three RPA subunits
(1). At least some plants
(e.g. rice) and some protists (e.g. Cryptosporidium parvum)
contain multiple genes encoding for subunits of RPA
(5,
6). In rice, there is evidence
for multiple RPA complexes that are thought to perform different cellular
functions (5). In contrast,
only a single alternative form of RPA2, called RPA4, has been identified in
humans (7). RPA4 was originally
identified as a protein that interacts with RPA1 in a yeast two-hybrid screen
(7). The RPA4 subunit is 63%
identical/similar to RPA2. Comparison of the sequences of RPA4 and RPA2
suggests that the two proteins have a similar domain
organization.4 RPA4
appears to contain a putative core DNA-binding domain (DBD G) flanked by a
putative N-terminal phosphorylation domain and a C terminus containing a
putative winged-helix domain (Fig.
1A). The RPA4 gene is located on the X
chromosome, intronless, and found mainly in
primates.4 Initial
characterization of RPA4 by Keshav et al.
(7) indicated that either RPA2
or RPA4, but not both simultaneously, interacts with RPA1 and RPA3 to form a
complex. This analysis also showed that RPA4 is expressed in placenta and
colon tissue but was either not detected or expressed at low levels in most
established cell lines examined
(7).Open in a separate windowFIGURE 1.Properties of aRPA complex. A, schematic diagram of the
structural and functional domains of the three subunits of RPA and (proposed
for) RPA4: DNA-binding domains (DBD A-G), the phosphorylation domain
(PD), winged-helix domain (WH), and linker regions
(lines). The sequence similarity between RPA2 and RPA4 is indicated
for each domain of the subunit. B, gel analysis of 2 μg of RPA4/3,
RPA. or aRPA separated on 8-14% SDS-PAGE gels and visualized by Coomassie Blue
staining. The position of each RPA subunit is indicated. C,
hydrodynamic properties of aRPA and RPA complexes. The sedimentation
coefficient and Stokes'' radius were determined as described previously by
sedimentation on a 15-35% glycerol gradient and chromatography on a Superose 6
10/300 GL column (GE Healthcare), respectively
(13). Mass and frictional
coefficients were calculated using the method of Siegal and Monty
(8). The predicted mass was
based upon the amino acid sequence derived from the DNA sequence.These studies describe the purification and functional analysis of an
alternative RPA (aRPA) complex containing RPA1, RPA3, and RPA4. The aRPA
complex is a stable heterotrimeric complex similar in size and stability to
the canonical RPA complex (RPA1, RPA3, and RPA2). aRPA interacts with ssDNA in
a manner indistinguishable from canonical RPA; however, it does not support
DNA replication in vitro. Mixing experiments demonstrate that aRPA
also inhibits canonical RPA from functioning in DNA replication. Hybrid
protein studies paired with structural modeling have allowed for the
identification of two regions of RPA4 responsible for this inhibitory
activity. Data presented here are consistent with recent analyses of RPA4
function in human
cells,4 and we
conclude that RPA4 has anti-proliferative properties and has the potential to
play a regulatory role in human cell proliferation through the control of DNA
replication. 相似文献
10.
Kevin Reinert Member HERA Editorial Board Larry Andrews Russell Keenan 《人类与生态风险评估》2006,12(5):811-818
Not a day passes where nanotechnology does not make headlines in the popular press, scientific journals, as well as in the regulatory arena. Environmental and public health activists are voicing a growing concern and focus on the risks potentially posed by nanotechnology and the ability of the government to regulate these new and exciting technologies. Whereas such concerns state the need for stringent, precautionary, and almost exclusionary approaches to the regulation of nanotechnology, many entities believe that a voluntary approach to these often novel materials and technologies is the appropriate and sensible path. In this editorial, we discuss the importance of nanotechnology, who cares, and the available options for approaching the regulation of this often novel technology. We focus on the U.S. Environmental Protection Agency (USEPA) and its voluntary regulatory data submission program as the preferred alternative. 2 相似文献
11.
《The Western journal of medicine》1962,97(3):195
The total number of non-federal* physicians in California rose from 23,065 in mid-1959 to 26,271 in January, 1962, an 11.3 per cent increase. The proportion of physicians in private active practice remained almost constant during this period.A significant rise, both in number and proportionally, took place in the full-time specialty category, offset by losses in the general practice-part-time specialty group. While specialists increased by over 30 per cent, general practitioners, who made up 31.7 per cent of all non-federal physicians in 1959, were only 24.7 per cent of the total in early 1962. 相似文献
12.
Suneeti Rekhari 《Visual Anthropology: Published in cooperation with the Commission on Visual Anthropology》2013,26(2):125-135
Throughout the latter half of the past century, cinema played a significant role in the shaping of the core narratives of Australia. Films express and implicitly shape national images and symbolic representations of cultural fictions in which ideas about Aboriginal identity have been embedded. In this article, 1 exclusionary practices in Australian narratives are analyzed through examples of films representing Aboriginal identity. Through these filmic narratives the articulation, interrogation, and contestation of views about filmic representations of Aboriginal identity in Australia are illuminated. The various themes in the filmic narratives are examined in order to compare and contrast the ways in which Australian films display the operation of narrative closure and dualisms within the film texts. 相似文献
13.
Clarice Ehlers Peixoto 《Visual Anthropology: Published in cooperation with the Commission on Visual Anthropology》2013,26(2):112-124
This article 1 focuses on the making of a family film and its transformation into a historical artifact. The conversations with my grandmother about her participation in the Gaucho Revolution (south of Brazil, 1923), which were recorded to be transmitted later on to our family, led me to research these historical facts in the public archives, sifting out documents from those days (newspapers, reports, and photographs) that could objectify her stories and her subjective images and especially allow the discovery of all possible relations between an individual memory and a collective memory. That implied building a speech and telling a story from only one family member's point of view, the grandmother's. More than that, it involved breaking with the family's inner-circle projections and presenting the film to a wider public, thus turning private images into public ones. 相似文献
14.
The quadrupole moment of formaldazine, H2C=N-N=CH2, has been studied for the trans structure (Ð(C-N-N-C) = = 180) and a series of gauche structures ( > 120). Restricted Hartree-Fock theory, second-order Møller-Plesset theory, and quadratic CI theory have been used in conjunction with the basis sets 6-31G*, 6-31G**, 6-311G** and 6-311++G**. Formaldazine is a quadrupolar molecule with primitive quadrupole moment tensor components of Q
xx
= -22.4, Q
yy
= -20.4 and Q
zz
= -25.6 DÅ at the theoretical level QCISD/6-311++G**. The examination of the theoretical level dependency shows that the reliable computation of a quadrupole moment requires the use of a flexible basis set. A large part of the component Q
zz
= -25.6 DÅ is due to the -system and compares, on a per electron basis, with the Q
zz
value of benzene. Conformational changes of the azines in the range 120° < < 180 have but a minute effect on the energy and are associated with only minor electronic relaxation. These conformational changes alter the quadrupole moment tensor components less than Q
xx
= +0.4, Q
yy
= +1.6 and Q
zz
= -1.0 DÅ at QCISD/6-311++G**//QCISD/6-31G*. The direction of these changes is explained by consideration of the rotation of the CN--systems and a small reduction of the CN bond polarity in the gauche structures. The Q
zz
component of formaldazine is representative of the quadrupole moment tensor component along the direction of the C
2
axis of the azine bridge as such. Hence, the results of this study suggest that azines can engage in strong quadrupole-quadrupole interactions and can be employed as lateral synthons in crystal engineering. Electronic Supplementary Material available. 相似文献
15.
Eugene M. Zubin Sergey I. Antsypovich Tatiana S. Oretskaya Elena A. Romanova Eugene M. Volkov Vadim N. Tashlitsky 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):425-440
Abstract The synthesis of modified oligodeoxyribonucleotides# containing 2′-amino-2′-deoxyarabinoadenosine residues (aAn) was carried out by means of the standard phosphoramidite chemistry. A high reactivity of such compounds to electrophilic reagents was shown. The cross-link formation between 2′-amino group of aAn and carboxyl function introduced into complementary strands occurs with 55% yield. The aAn residues was shown to induce the increased resistance of modified oligomers towards the enzymatic cleavage and provide the insignificant destabilization of DNA duplexes. 相似文献
16.
A new genus of oribatid mites of the family Tetracondylidae, Umashtanchaeviella
gen. n., with type species Umashtanchaeviella plethotricha
sp. n., is proposed and described from forest litter, the Bu Gia Map National Park, southern Vietnam. The new genus is distinguishable from other otocepheoid genera by the presence of notogastral plethotrichy.1 相似文献
17.
Ruben Heleno Cristina Garcia Pedro Jordano Anna Traveset José Maria Gómez Nico Blüthgen Jane Memmott Mari Moora Jorge Cerdeira Susana Rodríguez-Echeverría Helena Freitas Jens M. Olesen 《Biology letters》2014,10(1)
In recent years, the analysis of interaction networks has grown popular as a framework to explore ecological processes and the relationships between community structure and its functioning. The field has rapidly grown from its infancy to a vibrant youth, as reflected in the variety and quality of the discussions held at the first international symposium on Ecological Networks in Coimbra—Portugal (23–25 October 2013). The meeting gathered 170 scientists from 22 countries, who presented data from a broad geographical range, and covering all stages of network analyses, from sampling strategies to effective ways of communicating results, presenting new analytical tools, incorporation of temporal and spatial dynamics, new applications and visualization tools.1 During the meeting it became evident that while many of the caveats diagnosed in early network studies are successfully being tackled, new challenges arise, attesting to the health of the discipline. 相似文献
18.
19.
The following address was given by Dr. Cecil J. Watson at the Wm. J. Kerr Gold Headed Cane Lecture, University of California School of Medicine, on 9 June 1967. At this event on the eve of Commencement Day, the senior student who has been chosen by his classmates and by his professors in the Department of Medicine as the one who best exemplifies the qualities of a true physician is awarded a gold-headed cane.* This carries on the British tradition of a similar cane that was passed from physician to physician from 1689 to 1825. The original cane, which was carried successively by Doctors John Radcliffe, Richard Mead, Anthony Askew, David Pitcairn and Matthew Baillie, now rests in the Hall of the Royal College of Physicians in London. 相似文献
20.
Nanako Masada Antonio Ciruela David A. MacDougall Dermot M. F. Cooper 《The Journal of biological chemistry》2009,284(7):4451-4463
Nine membrane-bound mammalian adenylyl cyclases (ACs) have been identified.
Type 1 and 8 ACs (AC1 and AC8), which are both expressed in the brain and are
stimulated by Ca2+/calmodulin (CaM), have discrete neuronal
functions. Although the Ca2+ sensitivity of AC1 is higher than that
of AC8, precisely how these two ACs are regulated by Ca2+/CaM
remains elusive, and the basis for their diverse physiological roles is quite
unknown. Distinct localization of the CaM binding domains within the two
enzymes may be essential to differential regulation of the ACs by
Ca2+/CaM. In this study we compare in detail the regulation of AC1
and AC8 by Ca2+/CaM both in vivo and in vitro and
explore the different role of each Ca2+-binding lobe of CaM in
regulating the two enzymes. We also assess the relative dependence of AC1 and
AC8 on capacitative Ca2+ entry. Finally, in real-time fluorescence
resonance energy transfer-based imaging experiments, we examine the effects of
dynamic Ca2+ events on the production of cAMP in cells expressing
AC1 and AC8. Our data demonstrate distinct patterns of regulation and
Ca2+ dependence of AC1 and AC8, which seems to emanate from their
mode of regulation by CaM. Such distinctive properties may contribute
significantly to the divergent physiological roles in which these ACs have
been implicated.Nine membrane-bound mammalian adenylyl cyclases
(ACs),2 AC1–AC9,
have been identified (1). They
possess a common predicted structure
(2)3
and are stimulated by forskolin (FSK; except AC9) and Gsα,
although they are distributed and regulated differently
(1,
3,
4). Four ACs are regulated by
physiological concentrations of Ca2+ and thereby provide a critical
link between the Ca2+- and cAMP-signaling pathways
(3,
5); AC5 and AC6 are directly
inhibited by Ca2+, whereas AC1 and AC8 are stimulated by
Ca2+ in a calmodulin (CaM)-dependent manner
(5). AC3 is also regulated by
CaM in vitro, although this requires supramicromolar concentration of
Ca2+ (6), and in
vivo AC3 is inhibited by Ca2+ via CaM kinase II
(7), unlike AC1 and AC8.AC1 is closely related in sequence to the Ca2+/CaM-stimulable
rutabaga AC from Drosophila, which is important in
Drosophila learning tasks
(8–10).
AC1 and the other Ca2+/CaM-stimulable mammalian AC, AC8, have also
been implicated in learning and memory
(11). As a means of
establishing their proposed roles, single and/or double AC1 and AC8 knockout
mice have been generated. Mouse models have demonstrated that
Ca2+/CaM-stimulable ACs are involved in long-term potentiation and
long-term memory (12).
However, despite the general view that AC1 and AC8 can behave similarly,
discrete physiological actions of each isoform are becoming apparent. Recent
studies by Zhuo''s group demonstrated that AC1 specifically participates in
N-methyl-d-aspartic acid receptor-induced neuronal
excitotoxicity (13) and an
increase in GluR1 synthesis induced by blocking AMPA receptors
(14). Furthermore, Nicol and
colleagues (15,
16) showed a contribution of
AC1, but not AC8, in axon terminal refinement in the retina. On the other
hand, AC8 specifically was seen to be responsible for retrieval from adaptive
presynaptic silencing (17) and
the acquiring of new spatial information
(18). These differences in
physiological roles must reflect not only differences in their distributions
but also presumably in their regulatory properties. Both enzymes are expressed
in brain; AC1 is neuro-specific, whereas the expression of AC8 is more
widespread (1,
12). Within the central
nervous system, AC1 is abundant in the hippocampus, the cerebral cortex, and
the granule cells of the cerebellum, whereas AC8 has a high expression level
in the thalamus and the cerebral cortex
(19). Studies of mouse brain
revealed that AC1 is distributed pre-synaptically and AC8 post-synaptically
(18,
20).Although physiological differences in the roles of these two enzymes are
suggested from the studies outlined above, the regulatory mechanisms that
might underlie these differences are not. AC1 is more sensitive to
Ca2+ than is AC8 in vitro
(21,
22), yet details on how these
two enzymes are regulated by Ca2+/CaM are sparse. In non-excitable
cells, a Ca2+ elevation caused by capacitative Ca2+
entry (CCE), the mode of Ca2+ entry triggered by emptying
Ca2+ from internal stores
(23), preferentially
stimulates AC1 and AC8 (21).
Although stimulation of AC8 by CCE has been shown to be at least partially
dependent on its localization at lipid rafts
(24), whether AC1 is also
targeted to this region of plasma membranes has never been addressed. In
addition, CaM regulation of AC1 and AC8 has not been compared in detail,
although CaM appears to bind to different domains of the two enzymes. AC8
utilizes two CaM binding domains: a classic amphipathic “1-5-8-14”
motif at the N terminus and an IQ-like motif in the C2b domain
(25). A recent study indicates
that CaM pre-associates with the N terminus of AC8, where it becomes fully
saturated upon a Ca2+ rise, and activates the enzyme via a
C-terminally mediated relief of auto-inhibitory mechanisms
(26). By contrast, only
residues 495–522 of the C1b region of AC1 have been shown to bind CaM in
a Ca2+-dependent manner
(27,
28). With the presence of only
one CaM binding domain in AC1, a simpler mechanism of CaM regulation might be
expected.CaM mediates the regulation of numerous Ca2+-dependent processes
in eukaryotic cells (29). The
protein possesses N- and C-terminal lobes, both of which contain two
Ca2+ binding EF hands (EF1 and EF2 in the N lobe, and EF3 and EF4
in the C lobe (30)). Mutations
in the EF hands have been valuable for investigating the interaction of CaM
with its targets. Alanine substitutions in the EF12 pair or EF34 pair have
generated CaM12 and CaM34 to investigate the independent
function of the C and N lobes of CaM, respectively
(31,
32).Against the background of the distinct physiological roles carried out by
AC1 and AC8, we performed a detailed comparison of the two enzymes expressed
in HEK 293 cells. Their sensitivity to Ca2+/CaM was compared both
in vitro and in vivo; the possibility that they might be
expressed in different domains of the plasma membrane was addressed; and
putative lobe-specific CaM regulation was assessed using
Ca2+-binding mutants of CaM. Single cell measurements using a
FRET-based cAMP sensor were performed to compare the kinetic responses of the
enzymes to physiological elevations of [Ca2+]i.
The results demonstrate superficial similarities in the regulation of AC1 and
AC8 but critical disparities in their mechanism of activation by the lobes of
CaM and in the speed and pattern of their responsiveness to
[Ca2+]i. These discrete behaviors provide a
physiological opportunity for different outcomes to elevation of
[Ca2+]i, depending on the AC that is expressed
in particular contexts. 相似文献