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Results for “Protein Isoforms”

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PubMed1996

A non-AUG translational initiation event generates novel WT1 isoforms.

The Wilms' tumor (WT) suppressor gene, WT1, is mutated in a small set of WTs and is essential for proper development of the urogenital system. The gene has three sites of transcriptional initiation and produces mRNA transcripts containing 5'-untranslated regions of more than 350 nucleotides. The mRNA, through two alternative splicing events, is predicted to direct the synthesis of four protein isoforms with molecular masses of 47-49 kDa. In this report, we identify and characterize novel WT1 protein isoforms having predicted molecular masses of 54-56 kDa. Mutational analysis of the murine wt1 mRNA demonstrates that the novel isoforms are the result of translation initiation at a CUG codon 204 bases upstream of and in frame with the initiator AUG. We show that these isoforms are present in both normal murine tissue and in WTs. Like WT1, the larger isoforms localize to the cell nucleus and are capable of mediating transcriptional repression. Our results indicate that regulation of WT1 gene expression is more complex than previously suspected and have important implications for normal and abnormal urogenital system development.

Amino Acid Sequence↗

PubMed1998

Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms.

Catenins were discovered as proteins that are linked to the cytoplasmic domain of transmembrane cadherins. Among these junctional plaque proteins are several members of the Armadillo gene family: beta-catenin, plakoglobin, and p120ctn. Recently it became clear that some catenins also mediate nuclear signaling. We performed a detailed analysis of the human p120ctn gene (HGMW-approved symbol CTNND1) and its transcripts. The human p120ctn gene comprises 21 exons, potentially encoding up to 32 protein isoforms as products of alternative splicing. Human isoforms, designated 1 to 4, differ from each other by the start codon used. Additional isoforms are derived from combinations with alternatively used exons A (exon 18) and B (20), near the end of the open reading frame, and also with exon C (11) in the middle of the open reading frame. Hence, the longest isoform is of type 1ABC and comprises 968 amino acid residues. The functional consequence of the observed multitude of p120ctn splice variants awaits further study, but tissue-specific expression was obvious. Further, we demonstrate that the exon organization, which is not simply related to the Armadillo repeat structure, is very well conserved between the p120ctn gene and the related ARVCF gene, but not at all between these two genes and the beta-catenin or plakoglobin genes. The present data favor the concept that p120ctn is the prototype of a subfamily of Armadillo proteins, comprising ARVCF, p0071, delta-catenin/NPRAP, and plakophilins 1 and 2, that are more related to each other than to other Armadillo proteins.

Alternative Splicing↗

PubMed2004

Function of alternative splicing.

Alternative splicing is one of the most important mechanisms to generate a large number of mRNA and protein isoforms from the surprisingly low number of human genes. Unlike promoter activity, which primarily regulates the amount of transcripts, alternative splicing changes the structure of transcripts and their encoded proteins. Together with nonsense-mediated decay (NMD), at least 25% of all alternative exons are predicted to regulate transcript abundance. Molecular analyses during the last decade demonstrate that alternative splicing determines the binding properties, intracellular localization, enzymatic activity, protein stability and posttranslational modifications of a large number of proteins. The magnitude of the effects range from a complete loss of function or acquisition of a new function to very subtle modulations, which are observed in the majority of cases reported. Alternative splicing factors regulate multiple pre-mRNAs and recent identification of physiological targets shows that a specific splicing factor regulates pre-mRNAs with coherent biological functions. Therefore, evidence is now accumulating that alternative splicing coordinates physiologically meaningful changes in protein isoform expression and is a key mechanism to generate the complex proteome of multicellular organisms.

Alternative Splicing↗

PubMed1991

Two isoforms of the muscle acetylcholine receptor alpha-subunit are translated in the human cell line TE671.

We have previously reported the existence of 2 forms of mRNA for the human muscle acetylcholine receptor (AChR) alpha-subunit, thought to be generated by alternate splicing of a primary transcript and to encode 2 alpha-subunit protein isoforms. The 2 predicted alpha-subunit isoforms, differing by the insertion of 25 amino acids at position 58/59, have been synthesized from cRNA transcripts using rabbit reticulocyte lysates; these protein isoforms could be differentiated by immunoprecipitation using antibodies raised against synthetic peptides. The antibodies were used to demonstrate translation of both AChR alpha-subunit isoforms in the rhabdomyosarcoma (muscle) cell line TE671, in an approximate 1:1 ratio.

Amino Acid Sequence↗

PubMed2001

Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal.

Activation of protein kinase C (PKC) by phorbol ester facilitates hormonal secretion and transmitter release, and phorbol ester-induced synaptic potentiation (PESP) is a model for presynaptic facilitation. A variety of PKC isoforms are expressed in the central nervous system, but the isoform involved in the PESP has not been identified. To address this question, we have applied immunocytochemical and electrophysiological techniques to the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) of rat auditory brainstem. Western blot analysis indicated that both the Ca(2+)-dependent "conventional" PKC and Ca(2+)-independent "novel" PKC isoforms are expressed in the MNTB. Denervation of afferent fibers followed by organotypic culture, however, selectively decreased "novel" epsilon PKC isoform expressed in this region. The afferent calyx terminal was clearly labeled with the epsilon PKC immunofluorescence. On stimulation with phorbol ester, presynaptic epsilon PKC underwent autophosphorylation and unidirectional translocation toward the synaptic side. Chelating presynaptic Ca(2+), by using membrane permeable EGTA analogue or high concentration of EGTA directly loaded into calyceal terminals, had only a minor attenuating effect on the PESP. We conclude that the Ca(2+)-independent epsilon PKC isoform mediates the PESP at this mammalian central nervous system synapse.

Animals↗

PubMed2006

DNA binding properties of TAF1 isoforms with two AT-hooks.

TATA-binding protein-associated factor 1 (TAF1) is an essential component of the general transcription factor IID (TFIID), which nucleates assembly of the preinitiation complex for transcription by RNA polymerase II. TATA-binding protein and TAF1.TAF2 heterodimers are the only components of TFIID shown to bind specific DNA sequences (the TATA box and initiator, respectively), raising the question of how TFIID localizes to gene promoters that lack binding sites for these proteins. Here we demonstrate that Drosophila TAF1 protein isoforms TAF1-2 and TAF1-4 directly bind DNA independently of TAF2. DNA binding by TAF1 isoforms is mediated by cooperative interactions of two identical AT-hook motifs, one of which is encoded by an alternatively spliced exon. Electrophoretic mobility shift assays revealed that TAF1-2 bound the minor groove of adenine-thymine-rich DNA with a preference for the sequence AAT. Alanine-scanning mutagenesis of the alternatively spliced AT-hook indicated that Lys and Arg residues made essential DNA contacts, whereas Gly and Pro residues within the Arg-Gly-Arg-Pro core sequence were less important for DNA binding, suggesting that AT-hooks are more divergent than previously predicted. TAF1-2 bound with variable affinity to the transcription start site of several Drosophila genes, and binding to the hsp70 promoter was reduced by mutation of a single base pair at the transcription start site. Collectively, these data indicate that AT-hooks serve to anchor TAF1 isoforms to the minor groove of adenine-thymine-rich Drosophila gene promoters and suggest a model in which regulated expression of TAF1 isoforms by alternative splicing contributes to gene-specific transcription.

AT-Hook Motifs↗

PubMed2001

All three splice variants of the human sarco/endoplasmic reticulum Ca2+-ATPase 3 gene are translated to proteins: a study of their co-expression in platelets and lymphoid cells.

The molecular cloning of two previously unknown human sarco/endoplasmic reticulum Ca(2+)-ATPase 3 (SERCA3) 3'-end transcripts, 3b and 3c, has been recently published. Data were lacking, however, for the presence of these SERCA3 variants in different tissue or cell types at the protein level. Here we report the co-expression of three human SERCA3 protein isoforms in platelets and T lymphoid Jurkat cells. Isoform-specific polyclonal anti-peptide antibodies have been generated that recognize specifically the SERCA3a, 3b or 3c splice variants at their C-termini, and this has been confirmed by peptide-competition experiments as well. None of these antibodies cross-reacted with the housekeeping SERCA2b isoform co-expressed endogenously with SERCA3 proteins in non-muscle cells. Although all three SERCA3 isoforms could be detected in platelets, the 3a form was the most abundantly expressed species. Its size matched the apparent size of SERCA3a over-expressed in HEK-293 cells. Immunoprecipitation of the SERCA3 variants from platelet membranes using a PL/IM 430-affinity matrix provided evidence that the putative pan-anti-SERCA3 antibody, PL/IM 430, recognizes all SERCA3 protein isoforms. The epitope for the PL/IM 430 antibody could be localized in a 40 kDa N-terminal tryptic fragment common to all three SERCA3 variants. Comparative Western-blot analysis showed that the expression level of the SERCA3a, 3b and 3c isoforms was more than 10 times lower in Jurkat cells than in platelets, whereas expression of the ubiquitous SERCA2b was nearly identical. This work highlights new Ca(2+)-transporting proteins of haematopoietic cells and provides specific antibodies for their detection.

Alternative Splicing↗

PubMed1991

The roles of specific isoforms of protein kinase C in growth control and human colon cancer.

Protein kinase C (PKC) consists of a family of lipid-regulated enzymes which play a pivotal role in signal transduction. Studies with the cell line R6-PKC3, a derivative of R6 rat fibroblasts that overexpresses PKC beta 1, provide direct evidence that this isoform of PKC influences cell morphology, growth control, the production of an autocrine growth factor, and the action of an activated H-ras oncogene. Analysis of 32P-labelled phosphoproteins indicates that R6-PKC cells display increased phosphorylation of a 80/87 kDa protein (designated MARCKS), and after treatment with TPA they display a dramatic prolongation in the phosphorylation and in the cytosolic accumulation of this protein. These alterations in MARCKS may be responsible, at least in part, for the altered growth properties of R6-PKC3 cells. We have also examined the expression of endogenous isoforms of PKC in R6 cells and oncogene-transformed derivatives. Normal R6 cells express four isoforms of PKC, cPKC alpha, nPKC epsilon, nPKC delta, and nPKC zeta; nPKC delta and nPKC epsilon are the most abundant. nPKC epsilon and nPKC delta have an unusual distribution since 60-80% is membrane-bound. In response to TPA, the cytosolic levels of all four PKC isozymes were recruited to the membrane fraction. Prolonged treatment of R6 cells with TPA caused total loss of cPKC alpha, nPKC delta and nPKC zeta but only a 60% reduction in nPKC epsilon.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line, Transformed↗

PubMed2003

Altered CTX-catalyzed and endogenous [32P]ADP-ribosylation of stimulatory G protein alphas isoforms in postmortem bipolar affective disorder temporal cortex.

Reports of elevated Gs alpha subunit (alpha(s)) immunolabeling and cAMP-mediated hyper-functionality in autopsied cerebral cortical brain regions from bipolar affective disorder (BD) patients suggest signal transduction abnormalities occur in this disorder. Because covalent modification of alpha(s) can affect its turnover and levels, we determined whether CTX-catalyzed and endogenous [(32)P] adenosine diphosphate (ADP)-ribosylation of alpha(s) isoforms are altered in temporal and occipital cortical regions, which show elevated alpha(s) levels in BD as compared to nonpsychiatric subjects. Reduced CTX-catalyzed [(32)P]ADP-ribosylated alpha(s-S) and endogenous [(32)P]ADP-ribosylation of a 39-kDa alpha(s)-like protein were found in BD temporal cortex compared to controls. These findings suggest that clearance of these alpha(s) isoforms through ADP-ribosylation may be decreased in BD temporal cortex. Although no differences were observed in mean levels of endogenous and CTX-catalyzed [(32)P]ADP-ribosylation of alpha(s-L) in BD temporal cortex, alpha(s-L) immunolabeling was elevated significantly and correlated inversely with the degree of endogenous [(32)P]ADP-ribosylation of this subunit. In addition, endogenous [(32)P]ADP-ribosylation of an exogenous substrate, myelin basic protein, was similar in BD and comparison subject temporal cortex. Taken together, these observations suggest that elevations of alpha(s) in BD brain are more likely related to factors affecting the disposition or availability of alpha(s) to this posttranslational enzymatic modification.

Adenosine Diphosphate↗

PubMed1987

Slow-type C-protein in dystrophic chicken fast pectoralis muscle.

C-protein isoform expression in hereditary dystrophic chicken skeletal muscle was compared with that in normal chicken muscle during postnatal development by immunocytochemical and immunoblot methods. In the pectoralis muscle (PM) of both normal and dystrophic chicken, slow- and fast-type C-proteins were coexpressed in the vast majority of myofibers at neonatal age, but the slow C-protein disappeared, leaving continued expression of only the fast-type C-protein as muscle development progressed up to 2 weeks posthatch. In the dystrophic chicken PM, however, myofibers containing slow-type C-protein reappeared about 1 month posthatch and increased in number with the progression of muscular dystrophy. We conclude that C-protein isoform expression in dystrophic myofibers resembles that in neonatal myofibers and that the expression of slow-type C-protein can be seen as a marker for chicken muscular dystrophy.

Animals↗

PubMed2006

Calcium-dependent protein kinase isoforms in Petunia have distinct functions in pollen tube growth, including regulating polarity.

Calcium is a key regulator of pollen tube growth, but little is known concerning the downstream components of the signaling pathways involved. We identified two pollen-expressed calmodulin-like domain protein kinases from Petunia inflata, CALMODULIN-LIKE DOMAIN PROTEIN KINASE1 (Pi CDPK1) and Pi CDPK2. Transient overexpression or expression of catalytically modified Pi CDPK1 disrupted pollen tube growth polarity, whereas expression of Pi CDPK2 constructs inhibited tube growth but not polarity. Pi CDPK1 exhibited plasma membrane localization most likely mediated by acylation, and we present evidence that suggests this localization is critical to the biological function of this kinase. Pi CDPK2 substantially localized to as yet unidentified internal membrane compartments, and this localization was again, at least partially, mediated by acylation. In contrast with Pi CDPK1, altering the localization of Pi CDPK2 did not noticeably alter the effect of overexpressing this isoform on pollen tube growth. Ca(2+) requirements for Pi CDPK1 activation correlated closely with Ca(2+) concentrations measured in the growth zone at the pollen tube apex. Interestingly, loss of polarity associated with overexpression of Pi CDPK1 was associated with elevated cytosolic Ca(2+) throughout the bulging tube tip, suggesting that Pi CDPK1 may participate in maintaining Ca(2+) homeostasis. These results are discussed in relation to previous models for Ca(2+) regulation of pollen tube growth.

Base Sequence↗

PubMed2002

Expression pattern of dd4, a sole member of the d4 family of transcription factors in Drosophila melanogaster.

In vertebrates, three members of the d4 gene family code for proteins, which are believed to function as transcription factors and involved in regulation of various intracellular processes. One member of the family, ubi-d4/requiem is ubiquitously expressed gene and two other, neuro-d4 and cer-d4, are expressed predominantly in the neural tissues (Nucleic Acids Res. 20 (1992) 5579; Biochim. Biophys. Acta 14 (1992) 172; Mamm. Genome 11 (2000) 72; Mamm. Genome 12 (2001) 862). Typically, d4 proteins show distinct domain organisation with domain 2/3 in the N-terminal, Krüppel-type zinc finger in the central and two adjacent PHD-fingers (d4-domain) in the C-terminal part of the molecule. However, alternative splicing, which is responsible for complex expression patterns of both neurospecific members of the family, generates multiple protein isoforms lacking certain domains (Nucleic Acids Res. 20 (1992) 5579; Genomics 36 (1996) 174; Mamm. Genome 11 (2000) 72; Mamm. Genome 12 (2001) 862). Exact function of d4 proteins is unclear but their involvement in regulation of differentiation and apoptotic cell death has been proposed (J. Biol. Chem. 269 (1994) 29515; Mamm. Genome 11 (2000) 72; Mamm. Genome 12 (2001) 862). Here we identified a single gene, dd4, in the genome of Drosophila melanogaster, the protein product of which could be assigned to the d4 family. Expression of dd4 is regulated during Drosophila development, and is most prominent in syncytial embryos and later in the embryonic nervous and reproductive systems. In flies dd4 mRNA is found in most tissues but the highest level of expression is detected in ovaries.

Amino Acid Sequence↗

PubMed2000

Differential modulation of N-type 1B and P/Q-type 1A calcium channels by different G protein subunit isoforms.

Using transient calcium phosphate transfection into the human embryonic kidney tsa-201 cell line and subsequent whole-cell patch-clamp protocols, we examined the tonic modulation of cloned N- and P/Q-type calcium channels by five different G protein beta subunits via strong depolarizing voltage prepulses. For N- and P/Q-type channels, the magnitude of inhibition was dependent on the Gbeta subtype co-expressed. Both the absolute and relative magnitudes of Gbeta subunit-induced inhibition of P/Q-type channels differed from those observed with the N-type channel. For each calcium channel subtype, kinetics of both the prepulse-mediated recovery from inhibition and the re-inhibition following the prepulse were examined for each of the Gbeta subunits by varying either the duration between the pre- and the test pulse or the length of the prepulse. For each channel subtype, we observed a differential Gbeta subunit rank order with regard to the rates of re-inhibition and recovery from inhibition. On average, P/Q-type channels exhibited more rapid rates of recovery from inhibition than those observed with N-type channels. Different Gbeta subtypes mediated different degrees of slowing of activation kinetics. The differential modulation of P/Q- and N-type channels by various Gbeta subtypes may provide a mechanism for fine tuning the amount of calcium entering the presynaptic nerve termini.

Animals↗

PubMed1999

Purification, structural characterization, cloning and immunocytochemical localization of chemoreception proteins from Schistocerca gregaria.

Soluble low-molecular-mass protein isoforms were purified from chemosensory organs (antennae, tarsi and labrum) of the desert locust Schistocerca gregaria. Five genes encoding proteins of this group were amplified by PCR from cDNAs of tarsi and sequenced. Their expression products are polypeptide chains of 109 amino acids showing 40-50% sequence identity with putative olfactory proteins from Drosophila melanogaster and Cactoblastis cactorum. Direct structural investigation on isoforms purified from chemosensory organs revealed the presence in the expression products of two of the genes cloned. Two additional protein isoforms were detected and their molecular structure exhaustively characterized. MS analysis of all isoforms demonstrated that the four cysteine residues conserved in the polypeptide chain were involved in disulfide bridges (Cys29-Cys38 and Cys57-Cys60) and indicated the absence of any additional post-translational modifications. Immunocytochemistry experiments, performed with rabbit antiserum raised against the protein isoform mixture, showed selective labelling of the outer lymph in contact sensilla of tarsi, maxillary palps and antennae. Other types of sensilla were not labelled, nor were the cuticle and dendrites of the sensory cells. No binding of radioactively labelled glucose or bicarbonate was detected, in disagreement with the hypothesis that this class of proteins is involved in the CO2-sensing cascade. Our experimental data suggest that the proteins described here could be involved in contact chemoreception in Orthoptera.

Amino Acid Sequence↗

PubMed2001

A novel rat 523 amino acid phosphophoryn: nucleotide sequence and genomic organization.

Phosphophoryns (PP), the major noncollagenous proteins (NCPs) in dentin, are believed to play a crucial role in mineral nucleation and hydroxyapatite growth during dentin mineralization. Previously we identified two mature rat PP transcripts, one coding for a 240 amino acid protein (designated as PP(240)) (H.H. Ritchie, L.-H. Wang, J. Biol. Chem. 271 (1996) 21695-21698), and another coding for a 171 amino acid protein (PP(171)) (H. Ritchie, L. Wang, Biochim. Biophys. Acta 1493 (2000) 27-32). We now have identified a third novel dentin sialoprotein (DSP)-PP cDNA transcript that encodes a 523 amino acid protein (PP(523)) with typical PP characteristics including DSS and DS motifs suitable as potential casein kinase I and II phosphorylation sites. Based on amino acid composition, the PP(523) protein product is identical to native rat HP2. We also show that the PP(523) sequence is identical to the corresponding genomic DNA sequence. Taken together, the existence of multiple DSP-PP transcripts, each significantly different from the other in net negative charge, suggests that dentin mineralization processes may be under fine-tune control by these PP protein isoforms.

Amino Acid Sequence↗

PubMed1989

Developmental and muscle-specific regulation of avian fast skeletal troponin T isoform expression by mRNA splicing.

We have investigated the developmental regulation of the avian fast skeletal muscle troponin T (TnTf) gene of the Japanese quail. Sequence analysis of troponin T mRNA, cDNA clones, and a genomic DNA segment demonstrate that the avian, fast skeletal TnTf protein isoforms are produced from a single gene. This TnTf gene is expressed in skeletal muscle, but not in adult cardiac muscles or in non-muscle tissues. In addition to known TnT isoforms, three new isoforms of TnT are described. These isoforms arise by regulated alternative RNA splicing of exons in the 5' and 3' regions of TnTf transcripts. Alternative splicing of the 5' TnTf exons involves splicing of multiple exons in different combinations (i.e. not mutually exclusive), whereas 3' alternative splicing involves mutually exclusive splice choices between two exons (alpha or beta exons). S1 nuclease protection and primer extension analyses show that alternative splicing of both 5' and 3' exons is precisely regulated and coordinated in physiologically different striated muscles, which express distinct, restricted combinations of 5' and 3' alternatively spliced exons in mRNA transcripts. In contrast, different embryonic muscles and clonal embryonic myoblast cultures coexpress the 3' alternative splice choices. This indicates that alternative splicing of TnTf mRNAs is controlled in different adult muscles by specific trans factors, and not by the restricted expression of different spliced forms in different embryonic myoblast lineages. Comparison of TnTf isoform expression in quail and chicken flight muscle (Wilkinson, J. M., Moir, A. J., and Waterfield, M. D. (1984) Eur. J. Biochem. 143, 47-56) to TnTf isoforms of the rat (Breitbart, R. E., and Nadal-Ginard, B. (1986) J. Mol. Biol. 188, 313-324), and rabbit (Pearlstone, J. R., Carpenter, M. R., and Smillie, M. B. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 1902-1906) indicates that the avian gene contains an additional exon(s) not present in mammalian genes. The alternative exon sequences TnTf mRNAs expressed in anatomically distinct quail muscles can be correlated with sequences in TnTf protein isoforms in these chicken muscles. Thus, the regulated splicing of alternative exons in TnT transcripts, and not selective translation of stochastically spliced TnT mRNAs, regulates TnTf isoform expression in specific muscles.

Aging↗

PubMed1998

Induction of differentiation in normal human keratinocytes by adenovirus-mediated introduction of the eta and delta isoforms of protein kinase C.

Protein kinase C (PKC) plays a crucial role(s) in regulation of growth and differentiation of cells. In the present study, we examined possible roles of the alpha, delta, eta, and zeta isoforms of PKC in squamous differentiation by overexpressing these genes in normal human keratinocytes. Because of the difficulty of introducing foreign genes into keratinocytes, we used an adenovirus vector system, Ax, which allows expression of these genes at a high level in almost all the cells infected for at least 72 h. Increased kinase activity was demonstrated in the cells overexpressing the alpha, delta, and eta isoforms. Overexpression of the eta isoform inhibited the growth of keratinocytes of humans and mice in a dose (multiplicity of infection [MOI])-dependent manner, leading to G1 arrest. The eta-overexpressing cells became enlarged and flattened, showing squamous cell phenotypes. Expression and activity of transglutaminase 1, a key enzyme of squamous cell differentiation, were induced in the eta-overexpressing cells in dose (MOI)- and time-dependent manners. The inhibition of growth and the induction of transglutaminase 1 activity were found only in the cells that express the eta isoform endogenously, i.e., in human and mouse keratinocytes but not in human and mouse fibroblasts or COS1 cells. A dominant-negative eta isoform counteracted the induction of transglutaminase 1 by differentiation inducers such as a phorbol ester, 1alpha,25-dihydroxyvitamin D3, and a high concentration of Ca2+. Among the isoforms examined, the delta isoform also inhibited the growth of keratinocytes and induced transglutaminase 1, but the alpha and zeta isoforms did not. These findings indicate that the eta and delta isoforms of PKC are involved crucially in squamous cell differentiation.

Adenoviruses, Human↗

PubMed2004

Up-regulation of Na(+),K(+)-ATPase alpha 3-isoform and down-regulation of the alpha1-isoform in human colorectal cancer.

We investigated expression levels of Na(+),K(+)-ATPase alpha-isoforms and their ATPase activities in human colorectal cancer tissue and the accompanying normal mucosa. A decrease in expression of the alpha1-isoform protein was observed in all sampled cancer tissues compared with the normal mucosae. The level of ouabain (5 microM)-sensitive Na(+),K(+)-ATPase activity in carcinomas was 81+/-5% that of in the normal mucosae. The mRNA expression of alpha2- and alpha 4-isoforms was decreased in almost all the carcinoma samples. Interestingly, the expression level of the alpha 3-isoform protein in the cancer tissue was higher than that of the normal mucosa. These results indicate that a decrease in the alpha1-isoform expression and an increase in the alpha 3-isoform expression may be associated with colorectal cancer.

Asian People↗