一种新的蛋白酪氨酸磷酸酶基因的克隆、定位和组织表达谱研究

从人胎肝cDNA库分离出一长度为5248bp的cDNA克隆,该基因包含26个外显子和25个内含子,染色体定位于在某些肿瘤细胞中易缺失的3p21.1-21.33。其可读框编码1636个氨基酸,该蛋白属于蛋白酪氨酸磷酸酶（PTP）家族,其C端有一个典型的PTP结构域,N端含有约800氨基酸残基的BRO1样结构域及随后2个可能的SH3结构域结合位点,在这两个结构域之间及C末端还各有一个脯氨酸富集区。Northern杂交和点杂交分析显示,该基因以大约5.4kb的单一转录物广泛表达于人体各种组织,而且在人部分肿瘤细胞中高表达。结果提示,人源PTP－TD14是一个新的蛋白酪氨酸磷酸酶。     

A novel member of lymphocyte-specific protein tyrosine kinase protein identified in lamprey,Lampetrajaponica

Lymphocyte-specific protein tyrosine kinase p56 （Lck） is a member of the Src family of non-receptor protein tyrosine kinase. Lck plays an important role in mediating T-cell recep- tor （TCR） signal tmnsduction and the development, differenti- ation, proliferation, and activation of T-cells [ 1 ]. Lck contains N-terminus of myristylation sequence, a unique amino- terminus region, followed by Src homology 3 （SH3） and SH2 domains and a C-terminus oftyrosine kinase catalytic domain [2].     

The SHP—2 tyrosine phosphatase：Signaling mechanisms and biological functions

Cellular biological avtivities are tightly controlled by intracellular signaling processes initiated by extracellular signals.Protein tyrosine phosphatases,which remove phosphate groups from phosphorylated signaling molecules,play equally important tyrosine roles as protein tyrosine kinases in signal transduction.SHP-2 a cytoplasmic SH2 domain containing protein tyrosine phosphatase,is involved in the signaling pathways of a variety of growth factors and cytokines.Recent studies have clearly demonstrated that this phosphatase plays an important role in transducing signal relay from the cell surface to the nucleus,and is a critical intracellular regulator in mediating cell proliferation and differentiation.     

Shp2, a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia

Shp2, encoded by the PTPNll gene in human, is a ubiquitously expressed protein tyrosine phosphatase that contains two N-terminal Src homology 2 （SH2） domains （N-SH2, C-SH2, respectively）, a catalytic protein-tyrosine phosphatase （PTP） domain, and a C-terminal tail with tyrosyl phosphorylation sites and a prolyl-rich motif [1]. The progress of our understanding of biological functions of Shp2 has clearly shown that Shp2 plays an important role not only in biology of normal hematopoietic cells and other mammalian cells, but also in the development of leukemia and other tumors. Most recently, PTPNll gene has been firmly established as the first proto-oncogene that encodes a protein tyrosine phosphatase [1-3]. In the hematopoietic system, most if not all function of Shp2 is to act as a positive component that is essential for proliferation and/or survival of hematopoietic cells through regulation of signaling pathways involving Erk, Akt and STATS [ 1-4]. Over the past few years, a number of disease-associated Shp2 mutants have been identified in human leukemia and other malignancies [1, 3, 4]. Recently, studies from our laboratories and others strongly suggest that dysregulation of wild-type Shp2 enzyme may be involved in the pathogenesis of adult leukemia [4-7]. These findings not only provide new insights into the role of Shp2 in leukemogenesis and other tumors, but also suggest new therapeutic targets for anti-leukemia drugs.     

Cortactin mediated morphogenic cell movements during zebrafish (Danio rerio) gastrulation

Cortactin, a filamentous actin (F-actin) associated protein and a prominent substrate of protein tyrosine kinase Src[1,2], is composed of several functional do-mains, including an amino terminal domain (NTA) that is rich in acidic residues, six and one half 37-amino-acid tandem repeating segments, an al-pha-helical motif, a less conserved region but rich in tyrosine, proline, serine and threonine residues, and a Src homology 3 (SH3) domain at the distal carboxyl terminus. In mammalian cells …     

Cloning and identification of a novel RNF6 transcriptional splice variant Spg2 in human development

RING finger proteins are zinc finger proteins containing the RING motifs. They act mainly as E3 ubiq-uitin ligases, bind the ubiquitin E2 conjugating enzyme and promote degradation of targeted proteins, Many novel genes have been isolated and differentially expressed in human adult and embryo testis by a testis cDNA-array differential display technique. A novel RING finger cDNA is highly expressed in adult testis and at low level in fetal testis. It was named Spg2. It contains a 2055 nucleotide ORF, en-codes a 685-amino-acid RNF6 protein, and has a RING finger in its C terminal. NCBI Blast shows that the gene is located on chromosome 13 and contains five exons. A multiple tissue expression profile also indicates that it is highly expressed in human testis, so we speculate that it may be associated with human spermatogenesis by virtue of the action of its RING domain.