Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify genes involved in signal transduction pathways that regulate T cell activation and development, murine fetal thymocytes were screened for expression of protein tyrosine kinase family members by the polymerase chain reaction. Using this approach, a non-receptor protein tyrosine kinase, txk, was identified and cloned. Tsk is expressed in thymocytes as early as fetal day 13.5 and its expression at the mRNA level continues throughout development. Txk transcripts are present in thymocytes, peripheral T cells and mast cell lines, but are not detectable in B cell macrophage/monocyte cell lines or in non-hematopoietic fetal or adult tissues. In both thymocytes and T cells, txk transcripts are down-regulated after activation with PMA and ionomycin, concanavalin A or T cell receptor cross-linking. Sequence analysis indicates that txk contains SH2, SH3 and kinase catalytic domains and belongs to the tec family of cytoplasmic protein tyrosine kinases which includes tec, itk and btk. Its unique N-terminus contains a proline-rich region, but unlike the other tec family members, does not contain a pleckstrin homology domain. The restricted expression pattern of txk and its regulation by T cell activation make it an excellent candidate for involvement in signal transduction during thymocyte development.
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PMID:Murine txk: a protein tyrosine kinase gene regulated by T cell activation. 754 61

Among cytoplasmic protein-tyrosine kinases (PTKs) Tec now forms a novel subfamily with recently identified Tec-related PTKs (Btk and Itk/Tsk). Tec is known to be abundantly expressed in myeloid cells, and multiple forms of Tec protein can be generated via the mechanism of alternative splicing. In this report, we have investigated 5'-terminal diversity of the tec messages to demonstrate a predominant form of the Tec protein in mouse hematopoietic cell lines. Using anti-Tec serum, we could show that stimulation with interleukin-3 (IL-3) can induce tyrosine phosphorylation of Tec both in myeloid and pro-B-cell lines. IL-3 stimulation was also shown to induce kinase activity of Tec. Furthermore, we could demonstrate that Tec is constitutively associated with the Shc protein in vivo. Thus, we conclude that Tec is involved in the signaling pathway of IL-3.
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PMID:Tec protein-tyrosine kinase is involved in interleukin-3 signaling pathway. 781 91

Mouse Tec is a non-receptor type protein-tyrosine kinase and is highly expressed in many hematopoietic cell lines. To investigate the roles of the Tec kinase in the human hematopoietic system, we isolated cDNAs encoding the human Tec kinase. The human tec cDNAs can encode a peptide of 631 amino acid residues with a calculated molecular mass of 73,624. The predicted human Tec protein is highly homologous to those of the members of the Tec family including mouse Tec type IV (94% homology), mouse Tsk/Itk (60%), and human Btk (57%). The homology between human Tec and other members of the Tec family can be observed not only in the Src homology 3 (SH3), SH2, and kinase domains, but also in the N-terminal unique domain. Northern blot analysis demonstrated that the major transcripts of tec could be detected at 2.6 kb and 3.6 kb in a wide range of human hematopoietic cell lines including myeloid, B-, and T-cell lineages. Interestingly, high expression of the tec gene could be detected in all of the three patients examined with myelodysplastic syndrome. The human tec gene was mapped by fluorescence in situ hybridization (FISH) to chromosome 4p12.
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PMID:Molecular cloning and analysis of the human Tec protein-tyrosine kinase. 793 62

A gene for a novel, putative cytoplasmic tyrosine kinase, TXK has been isolated from a human peripheral blood cDNA library. The complete nucleotide sequence of the cDNA indicates that it is related most closely to EMT, a tyrosine kinase of T cells and to the B-cell tyrosine kinase Btk, which is mutated in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency disease (XID) in mouse. TXK, like BTK, is a member of the Tec sub-family of Src-type (non-receptor) tyrosine kinases. Like similar Tec sub-family members, and unlike the other Src kinases, TXK lacks both the N-terminal myristylation signal and the C-terminal regulatory tyrosine. TXK expression is detected primarily in T cells and some myeloid cell lines but not in a number of other cell types. TXK shares 60% amino acid homology with EMT and 57% with BTK over the SH3, SH2 (Src-homology) and catalytic domains but unlike BTK, EMT and tec, it lacks Gap 1 homology and steroid hormone receptor homology in the N-terminal region. Genomic clones containing TXK have been isolated and hybridize to chromosome position 4p12.
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PMID:TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12. 795 Dec 33

To identify tyrosine kinases that may regulate regeneration of the mammalian intestinal epithelium, we amplified portions of the catalytic domains of protein kinases expressed in intestinal crypt cells, using the polymerase chain reaction technique with primers directed against two invariant amino acid sequence motifs found in all kinases. These fragments were cloned and a library of kinase catalytic domains was generated. Sequence analysis of unique clones resulted in the identification of the catalytic domains of several characterized tyrosine kinases, including lyn, hck, c-fgr, tec, JAK2, itk, and the putative receptor kinase ryk, and expression of these kinases has not previously been described in the intestine. We compared the levels of mRNA encoding these kinases in multiple tissues using RNase protection assays, and we localized the expression of hck, lyn, and JAK2 in the intestine using in situ hybridization. In addition, we identified two novel putative catalytic domain sequences. One of these, which we have named sik (src-related intestinal kinase), is expressed at high levels in the gastrointestinal tract and may play a specific role in signal transduction in epithelial tissues.
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PMID:Tyrosine kinase gene expression in the mouse small intestine. 820 50

We cloned novel cDNAs from MB02 human erythroleukemia cells using PCR based approaches: a) Differential display by means of RT-PCR using one 5' primer CTTGATTGCC and four different 3' primers (T12AA, T12CA, T12GA, and T12AT). Ninety-three percent of the differential clones which were reamplified and sequenced were cDNAs of previously unidentified genes. b) Cloning using degenerate TFIIIA-like zinc finger domain specific oligonucleotide. Of the 54 clones sequenced, 20 contained two or more zinc finger sequences. Ten of these clones were new zinc finger cDNAs and one belonged to a known zinc finger gene (ZFP7). c) Cloning using degenerate tyrosine kinase(TK) domain-specific oligonucleotides corresponding to the highly conserved amino acid sequences IHRDLAA and DVWSFG. Of the 28 cDNA clones sequenced, 7 were JAK1 TK, one was atk TK, one was tec TK. The remaining sequences belonged to new ESTs or to ribosomal genes. d) Cloning using degenerate POU domain-specific oligonucleotides corresponding to sequence FK(QV)RRIK of the POU-specific domain and to sequence VWFCN(RQ)R of the POU-homeodomain. Sixteen clones were sequenced and all but one were identical with the Oct-1 transcriptional factor. Differential display RT-PCR and PCR-based cDNA cloning using degenerate primers for zinc finger motifs yielded the largest number of new genes expressed in MBO2 cells.
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PMID:Identification of new genes expressed in a human erythroleukemia cell line. 880 82

Pancreatic cancer remains one of the most difficult malignancies to treat. Minimal improvements in patient outcomes and persistently abysmal patient survival rates underscore the great need for new treatment strategies. Currently, there is intense interest in therapeutic strategies that target tyrosine protein kinases. Here, we employed kinome arrays and bioinformatic pipelines capable of identifying differentially active protein tyrosine kinases in different patient-derived pancreatic ductal adenocarcinoma (PDAC) cell lines and wild-type pancreatic tissue to investigate the unique kinomic networks of PDAC samples and posit novel target kinases for pancreatic cancer therapy. Consistent with previously described reports, the resultant peptide-based kinome array profiles identified increased protein tyrosine kinase activity in pancreatic cancer for the following kinases: epidermal growth factor receptor (EGFR), fms related receptor tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR-3), insulin receptor (INSR), ephrin receptor A2 (EPHA2), platelet derived growth factor receptor alpha (PDGFRA), SRC proto-oncogene kinase (SRC), and tyrosine kinase non receptor 2 (TNK2). Furthermore, this study identified increased activity for protein tyrosine kinases with limited prior evidence of differential activity in pancreatic cancer. These protein tyrosine kinases include B lymphoid kinase (BLK), Fyn-related kinase (FRK), Lck/Yes-related novel kinase (LYN), FYN proto-oncogene kinase (FYN), lymphocyte cell-specific kinase (LCK), tec protein kinase (TEC), hemopoietic cell kinase (HCK), ABL proto-oncogene 2 kinase (ABL2), discoidin domain receptor 1 kinase (DDR1), and ephrin receptor A8 kinase (EPHA8). Together, these results support the utility of peptide array kinomic analyses in the generation of potential candidate kinases for future pancreatic cancer therapeutic development.
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PMID:Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases. 3321 62

Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human diseases. In pancreatic ductal adenocarcinoma (PDAC), innovative pharmaceutical strategies such as kinase targeting have been unable to appreciably increase patient survival. This may be due, in part, to unchecked desmoplastic reactions to pancreatic tumors. Desmoplastic stroma enhances tumor development and progression while simultaneously restricting drug delivery to the tumor cells it protects. Emerging evidence indicates that many of the pathologic fibrotic processes directly or indirectly supporting desmoplasia may be driven by targetable protein tyrosine kinases such as Fyn-related kinase (FRK); B lymphoid kinase (BLK); hemopoietic cell kinase (HCK); ABL proto-oncogene 2 kinase (ABL2); discoidin domain receptor 1 kinase (DDR1); Lck/Yes-related novel kinase (LYN); ephrin receptor A8 kinase (EPHA8); FYN proto-oncogene kinase (FYN); lymphocyte cell-specific kinase (LCK); tec protein kinase (TEC). Herein, we review literature related to these kinases and posit signaling networks, mechanisms, and biochemical relationships by which this group may contribute to PDAC tumor growth and desmoplasia.
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PMID:Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia. 3323 70