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Intracellular Region (intracellular + region)

Distribution by Scientific Domains

Life Sciences	50%

Selected Abstracts

One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B,

HUMAN MUTATION, Issue 1 2003
Ali R. Afzal
Abstract Autosomal recessive Robinow syndrome (RRS) is a severe skeletal dysplasia with short stature, generalized limb shortening, segmental defects of the spine, brachydactyly, and a dysmorphic facial appearance. The gene encoding receptor orphan receptor tyrosine kinase 2 (ROR2) is located on chromosome 9q22 and homozygous loss-of-function mutations in this gene are responsible for RRS. Moreover, knocking out the mouse Ror2 gene causes mesomelic dwarfism in the homozygous state, with almost identical features to recessive Robinow syndrome. The protein product of this gene is a cell membrane receptor, containing distinct motifs including an immunoglobulin-like (Ig) domain, a Frizzled-like cysteine-rich domain (FRZ or CRD), and a kringle domain (KD) in the extracellular region; and an intracellular region with tyrosine kinase (TK), serine/threonine-rich, and proline-rich structures. The extracellular motifs of the ROR2 protein are known to be involved in protein,protein interactions. The tyrosine kinase domain is involved in an as yet uncharacterized signaling pathway. Interestingly, heterozygous mutations in ROR2 have recently been shown to give rise to autosomal dominant brachydactyly type B1 (BDB1). This condition is characterized by terminal deficiency of fingers and toes. A variety of mutations have been reported in ROR2. Here, these genetic defects are compiled and possible genotype,phenotype correlations are discussed. Hum Mutat 22:1,11, 2003. © 2003 Wiley-Liss, Inc. [source]

The influence of N-glycosylation and C-terminal sequence on secretion of HBV large surface antigen from S. cerevisiae

BIOTECHNOLOGY & BIOENGINEERING, Issue 2 2005
Jin-Seung Park
Abstract In Saccharomyces cerevisiae, we synthesized and secreted L-HBVsAg (named as pre-S(Met1 to Asn174)::S(Met175 to Ile400)) and three mutants, i.e., pre-S°°::S (Asn15Gln and Asn123Gln), pre-S°°::S° (Asn15Gln, Asn123Gln, and Asn320Gln), and pre-S°°::S°° (Asn15Gln, Asn123Gln, Asn233Gln, and Asn320Gln). All of the secreted pre-S::S was N-glycosylated, i.e., hyper-mannosylated. In the secretion of pre-S°°::S and pre-S°°::S°, besides the hyper-mannosylated form, another immunoreactive protein with much lower molecular mass was observed, which seems to be unglycosylated form of pre-S°°::S and pre-S°°::S°. Only a part of the secreted pre-S°°::S or pre-S°°::S° molecules was N-glycosylated, and the site for the partial N-glycosylation seems to be Asn233 in S-antigen region. Compared to the N-glycosylated pre-S°°::S and pre-S°°::S°, pre-S°°::S°° (non-N-glycosylated mutant) was secreted with lower secretion efficiency but showed apparent immunoreactivity to anti-S antigen monoclonal Ab. Interestingly, unlike pre-S°°::S°° with authentic C-terminus, the recombinant pre-S°°::S°° with C-terminal myc or poly-histidine tag (pre-S°°::S°°::tag) was almost all aggregated into insoluble proteins in the intracellular region. Conclusively, the C-terminal sequence and glycosylation in S-antigen region seem to be of crucial importance in determining the secretion efficiency of L-HBVsAg in S. cerevisiae. © 2005 Wiley Periodicals, Inc. [source]

Expression, crystallization and preliminary X-ray diffraction analysis of human paired Ig-like type 2 receptor , (PILR,)

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2008
Shigekazu Tabata
Human paired immunoglobulin-like (Ig-like) type 2 receptor , (PILR,) is a type I membrane protein that is mainly expressed in immune-related cells such as monocytes, granulocytes and dendritic cells. PILR, can suppress the functions of such immune cells because it has the immunoreceptor tyrosine-based inhibitory motif (ITIM) in the intracellular region, which recruits the phosphatase Src homology-2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP-2) to inhibit phophorylations induced by activation signals. The extracellular region of human PILR, comprises one immunoglobulin superfamily V-set domain and a stalk region. The V-set domain (residues 13,131) of human PILR, was overexpressed in Escherichia coli as inclusion bodies, refolded by rapid dilution and purified. The PILR, protein was successfully crystallized at 293,K using the sitting-drop vapour-diffusion method. The crystals diffracted to 1.3,Å resolution at SPring-8 BL41XU; they belong to space group P212121, with unit-cell parameters a = 40.4, b = 45.0, c = 56.9,Å, and contain one molecule per asymmetric unit. [source]

Non-solid oncogenes in solid tumors: EML4,ALK fusion genes in lung cancer

CANCER SCIENCE, Issue 12 2008
Hiroyuki Mano
It is generally accepted that recurrent chromosome translocations play a major role in the molecular pathogenesis of hematological malignancies but not of solid tumors. However, chromosome translocations involving the e26 transformation-specific sequence transcription factor loci have been demonstrated recently in many prostate cancer cases. Furthermore, through a functional screening with retroviral cDNA expression libraries, we have discovered the fusion-type protein tyrosine kinase echinoderm microtubule-associated protein like-4 (EML4),anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC) specimens. A recurrent chromosome translocation, inv(2)(p21p23), in NSCLC generates fused mRNA encoding the amino-terminal half of EML4 ligated to the intracellular region of the receptor-type protein tyrosine kinase ALK. EML4,ALK oligomerizes constitutively in cells through the coiled coil domain within the EML4 region, and becomes activated to exert a marked oncogenicity both in vitro and in vivo. Break and fusion points within the EML4 locus may diverge in NSCLC cells to generate various isoforms of EML4,ALK, which may constitute ~5% of NSCLC cases, at least in the Asian ethnic group. In the present review I summarize how detection of EML4,ALK cDNA may become a sensitive diagnostic means for NSCLC cases that are positive for the fusion gene, and discuss whether suppression of ALK enzymatic activity could be an effective treatment strategy against this intractable disorder. (Cancer Sci 2008; 99: 2349,2355) [source]