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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the cloning and molecular analysis of TRK2, the gene likely to encode the low-affinity K+ transporter in Saccharomyces cerevisiae. TRK2 encodes a protein of 889 amino acids containing 12 putative membrane-spanning domains (M1 through M12), with a large hydrophilic region between M3 and M4. These structural features closely resemble those contained in TRK1, the high-affinity K+ transporter. TRK2 shares 55% amino acid sequence identity with TRK1. The putative membrane-spanning domains of TRK1 and TRK2 share the highest sequence conservation, while the large hydrophilic regions between M3 and M4 exhibit the greatest divergence. The different affinities of TRK1 trk2 delta cells and trk1 delta TRK2 cells for K+ underscore the functional independence of the high- and low-affinity transporters. TRK2 is nonessential in TRK1 or trk1 delta haploid cells. The viability of cells containing null mutations in both TRK1 and TRK2 reveals the existence of an additional, functionally independent potassium transporter(s). Cells deleted for both TRK1 and TRK2 are hypersensitive to low pH; they are severely limited in their ability to take up K+, particularly when faced with a large inward-facing H+ gradient, indicating that the K+ transporter(s) that remains in trk1 delta trk2 delta cells functions differently than those of the TRK class.
Mol Cell Biol 1991 Aug
PMID:TRK1 and TRK2 encode structurally related K+ transporters in Saccharomyces cerevisiae. 207 19

A human epithelial (HeLa) cDNA library was screened with degenerate oligonucleotides designed to hybridize to highly conserved regions of protein-tyrosine kinases. One cDNA from this screen was shown to contain a putative protein-tyrosine kinase catalytic domain and subsequently used to isolate another cDNA from a human keratinocyte library that encompasses the entire coding region of a 976-amino-acid polypeptide. The predicted protein has an external domain of 534 amino acids with a presumptive N-terminal signal peptide, a transmembrane domain, and a cytoplasmic domain of 418 amino acids that includes a canonical protein-tyrosine kinase catalytic domain. Molecular phylogeny indicates that this protein kinase is closely related to eph and elk and that this receptor family is more closely related to the non-receptor protein-tyrosine kinase families than to other receptor protein-tyrosine kinases. Antibodies raised against a TrpE fusion protein immunoprecipitated a 130-kDa protein that became phosphorylated on tyrosine in immune complex kinase assays, indicating that this protein is a bona fide protein-tyrosine kinase. Analysis of RNA from 13 adult rat organs showed that the eck gene is expressed most highly in tissues that contain a high proportion of epithelial cells, e.g., skin, intestine, lung, and ovary. Several cell lines of epithelial origin were found to express the eck protein kinase at the protein and RNA levels. Immunohistochemical analysis of several rat organs also showed staining in epithelial cells. These observations prompted us to name this protein kinase eck, for epithelial cell kinase.
Mol Cell Biol 1990 Dec
PMID:cDNA cloning and characterization of eck, an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases. 217 5

Differential polypeptide expression in gene transfer cell lines of limited genetic complexity was analyzed as a gene mapping strategy. Subcellular fractionation preceding two-dimensional gel electrophoretic analysis simplified protein patterns and revealed subcellular location of differentially expressed polypeptides. As a model system, human MET oncogene polypeptide was identified in gene transfer lines by this approach. Genes encoding five putative human proteins were identified and provisionally assigned to chromosomal region 7q21-31 or to chromosome 1.
Somat Cell Mol Genet 1990 Jul
PMID:Polyacrylamide gel analysis of polypeptides in gene transfer cell lines. 221 22

We have studied mRNA levels for a variety of growth factors in biopsy specimens from malignant, benign and normal breast tissue. We found TGFb mRNA in all breast cancers and neoplastic breast tissues but the level of the TGFb mRNA were found to be higher in breast cancer (P = 0.01). TGFa mRNA was detected in a similar proportion of cancers as in neoplastic breast tissues but the TGFa receptor EGFR mRNA was detected in only 55% of breast cancers but in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inverted related to oestrogen receptor status and coexpression of TGFa and EGFR was observed in 28% of carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). PDGF a and b chain transcripts coexisted in all normal and malignant breast tissue. Insulin-like growth factor II mRNA was present in all 15 samples of non-malignant breast tissue but in only 11 of 21 (52%) of carcinomas.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Growth factor expression in breast tissue. 228 95

The primary structure of an insulin-like growth factor (IGF) binding protein produced by human HEP G2 hepatoma cells has been deduced from the cDNA sequence. The 234 amino acid protein has a predicted molecular mass of 25,274 and contains a single, distinctive cysteine-rich region. The N-terminal sequence of this protein is quite similar to the limited sequence data available for a rat IGF binding protein produced by BRL-3A cells and suggests a common ancestral origin. In contrast, the HEP G2 IGF binding protein sequence bears no similarity to the N-terminal 15 amino acids of a 53 kilodalton binding protein purified from human plasma. Comparison of full-length protein sequences for the IGF-I and IGF-II receptors with that of the HEP G2 IGF binding protein also fails to demonstrate any significant similarities among these three proteins, and suggests that each contains a unique binding domain for the IGF peptides.
Mol Endocrinol 1988 May
PMID:Insulin-like growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-I and IGF-II receptors. 245 22

N-terminal as well as internal amino acid sequence data were obtained from the GH dependent, insulin-like growth factor (IGF) binding protein, BP-53, purified from human plasma. Based on these sequence data, full-length cDNA clones of BP-53 have been isolated, and the complete deduced sequence of BP-53 determined. This sequence contains a 27 amino acid putative signal sequence followed by a mature protein of 264 amino acids containing 18 cysteine residues clustered near the N- and C-terminus. The deduced protein sequence of BP-53 has 33% amino acid identity including conservation of all 18 cysteine residues with the recently cloned BP-28, a smaller human IGF-binding protein identified in amniotic fluid and also secreted by the cell line HEP G2. Expression of the cloned BP-53 cDNA in mammalian tissue culture cells results in secretion of the protein into the culture medium. This expressed protein is identical to plasma-derived BP-53 in its immunoreactivity, high affinity binding of IGF-I and IGF-II, and mobility on sodium dodecyl sulfate gel electrophoresis.
Mol Endocrinol 1988 Dec
PMID:Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein. 246 30

The adenosine deaminase (ADA) locus appears to be under complex transcriptional control since levels of ADA enzyme activity vary greatly between different tissues and stages of development. Evidence that a trans-acting factor may be involved with the regulation of this locus came from previous experiments where fusion of ADA-negative human JEG cells and mouse ADA-positive cells led to the trans-activation of human ADA in a hybrid nucleus. Here, we demonstrate that the near euploid mouse embryo fibroblast cell line, CAK, also lacks detectable ADA enzyme activity due to altered gene regulation. We further demonstrate that ADA in CAK cells is not amenable to activation by somatic cell fusion. Following treatment with 5-azacytidine and Xyl-A selection (for ADA), however, CAK clones were obtained that stably express the ADA gene. Molecular analysis of the parental CAK cells and the ADA-positive derivative clones demonstrated that both 5' and 3' regions of the ADA gene had become hypomethylated in the ADA+ clones. We conclude that methylation is another element involved with the transcriptional control of the ADA gene and that ADA might serve as a useful model for studying the interaction of cis- and trans-acting regulational elements.
Somat Cell Mol Genet 1989 Jan
PMID:Hypomethylation and ADA gene expression in mouse CAK cells. 246 55

The insulin-like growth factor binding proteins (IGF-BPs) are structurally and immunologically distinct from the IGF type 1 or type 2 receptors and are characterized by two major forms: a large, GH-dependent BP found in human plasma (Mr = 150 k) and a small GH-independent BP (Mr = 28-42 k) present in human plasma, amniotic fluid, and HEP G2 cells. Using affinity cross-linking techniques, we have identified several binding proteins secreted by human breast cancer cell lines (Hs578T, MDA-231, T-47D, and MCF-7). Under nonreducing conditions these proteins migrated at an apparent Mr = 35, 28, 27, and 24 k, while reducing conditions revealed bands of apparent Mr = 35, 32, 27, and 24 k. Competitive binding studies in T-47D-conditioned media demonstrated that these BPs bound more IGF-II than IGF-I, and that IGF-II potently inhibited binding of either IGF-I or -II. Immunological studies using a polyclonal antibody against the HEP G2 small BP revealed no immunoreactive BP in conditioned media from MCF-7 and T-47D and only slight immunoreactivity in conditioned media from Hs578T and MDA 231. Analysis by Northern blot, using a probe from the cDNA sequence of the HEP G2 BP, demonstrated that Hs578T and MDA-231 cell lines contained small amounts of the 1.65 kilobase mRNA characteristic of the HEP G2 BP, while MCF-7 and T-47D tested negative.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Mar
PMID:Characterization of insulin-like growth factor binding proteins from human breast cancer cells. 247 92

Both cDNA clones and a genomic DNA clone encoding a 509-amino-acid protein that is 64% similar to chicken pp60c-src were isolated from the simple metazoan Hydra attenuata. We have designated this gene STK, for src-type kinase. Features of the amino acid sequence of the protein encoded by the STK gene suggest that it is likely to be myristoylated and regulated by phosphorylation in a manner similar to that found for pp60c-src. The genomic sequence encoding the protein was found to be interrupted by at least two introns, one of which was located in a position identical to that of one of the introns in the chicken src gene. The STK gene was expressed during early development of H. attenuata and at high levels in the epithelial cells of adult polyps. Probing of Hydra proteins with an antibody to phosphotyrosine indicated that the major phosphotyrosine-containing protein in H. attenuata may be the STK protein itself. H. attenuata is the simplest organism from which a protein-tyrosine kinase gene has been isolated. The presence of such a gene in the evolutionarily ancient phylum Cnidaria suggests that protein-tyrosine kinase genes arose concomitantly with or shortly after the appearance of multicellular organisms.
Mol Cell Biol 1989 Oct
PMID:Structure and expression of STK, a src-related gene in the simple metazoan Hydra attenuata. 247 20

Sequences of the plant-pathogenic Ti-plasmid were found to be constitutively expressed in LTK- and in HeLa-cells. Activity of the nopaline-synthase (nos) promoter in these cells was demonstrated by directing expression of G418 resistance from a connected neomycin-phosphotransferase II (NPT II) gene. Control transfections with the widely used thymidine-kinase (TK) promoter gave comparable transfection rates as found for the nos-promoter with NPT II. The function of the nos-promoter was also confirmed by assaying neomycin-phosphotransferase synthesized in cells containing a plasmid with the NPT II-gene under control of this promoter. Several LTK+ clones stably transfected with Ti-plasmid propagated the total Ti-plasmid DNA in a colinear state presumably as an episomal unit. Dot blot analysis and polymerase chain reaction showed predominant transcription of Ti-sequences from the T-DNA area reflecting transcriptional activity of this region not only in plant cells but also in animal cells. These results provide new information about promoter functions in systems unrelated to their natural environment.
Mol Cell Biochem 1989 Oct 05
PMID:Promoter activity and expression of sequences from Ti-plasmid stably maintained in mammalian cells. 248 9


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