Abstract:
:The 68 kDa Src substrate associated during mitosis (Sam68) is an RNA binding protein with Src homology (SH) 2 and 3 domain binding sites. We have recently found that Sam68 is a substrate of the insulin receptor (IR) that translocates from the nucleus to the cytoplasm and that Tyr-phosphorylated Sam68 associates with the SH2 domains of p85 PI3K and GAP, in vivo and in vitro. In the present work, we have further demonstrated the cytoplasmic localization of Sam68, which is increased in cells overexpressing IR. Besides, we sought to further study the association of Sam68 with the Ras-GAP pathway by assessing the interactions with SH3 domains of Grb2. We employed GST-fusion proteins containing the SH3 domains of Grb2 (N or C), and recombinant Sam68 for in vitro studies. In vivo studies of protein-protein interaction were assessed by co-immunoprecipitation experiments with specific antibodies against Sam68, GAP, Grb2, SOS, and phosphotyrosine; and by affinity precipitation with the fusion proteins (SH3-Grb2). Insulin stimulation of HTC-IR cells promotes phosphorylation of Sam68 and its association with the SH2 domains of GAP. Sam68 is constitutively associated with the SH3 domains of Grb2 and it does not change upon insulin stimulation, but Sam68 is Tyr-phosphorylated and promotes the association of GAP with the Grb2-SOS complex. In vitro studies with fusion proteins showed that Sam68 association with Grb2 is preferentially mediated by the C-terminal SH3 domains of Grb2. In conclusion, Sam68 is a substrate of the IR and may have a role as a docking protein in IR signaling, recruiting GAP to the Grb2-SOS complex, and in this way it may modulate Ras activity.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Najib S,Sánchez-Margalet Vdoi
10.1002/jcb.10198subject
Has Abstractpub_date
2002-01-01 00:00:00pages
99-106issue
1eissn
0730-2312issn
1097-4644journal_volume
86pub_type
杂志文章abstract::In the interphase nucleus of metazoan cells DNA is organized in supercoiled loops anchored to a nuclear matrix (NM). DNA loops are operationally classified in structural and facultative. Varied evidence indicates that DNA replication occurs in replication foci organized upon the NM and that structural DNA loops may co...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.24123
更新日期:2012-07-01 00:00:00
abstract::Plasminogen activator inhibitor type-1 (PAI-1) is the major negative regulator of the plasmin-dependent pericellular proteolytic cascade. PAI-1 gene expression is normally growth state regulated but frequently elevated in chronic fibroproliferative and neoplastic diseases affecting both stromal restructuring and cellu...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.20885
更新日期:2006-10-01 00:00:00
abstract::Acetylation of histones leads to conformational changes of DNA. We have previously shown that the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), induced cell cycle arrest, differentiation, and apoptosis. In addition to their antitumor effects as single agents, HDAC inhibitors may cause c...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.20045
更新日期:2004-05-15 00:00:00
abstract::The SON protein is a ubiquitously expressed DNA- and RNA-binding protein primarily localized to nuclear speckles. Although several early studies implicated SON in DNA-binding, tumorigenesis and apoptosis, functional significance of this protein had not been recognized until recent studies discovered SON as a novel RNA...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.24672
更新日期:2014-02-01 00:00:00
abstract::Procollagen (Type I) contains a noncollagenous COOH-terminal propeptide (C-propeptide) hypothesized to be important in directing chain association and alignment during assembly. We previously expressed human pro-alpha2(I) cDNA in rat liver epithelial cells, W8, that produce only pro-alpha1(I) trimer collagen (Lim et a...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract::Osteogenic differentiation refers to the process of bone formation and remodeling, which is controlled by complex molecular mechanisms. Activin A receptor type I (ACVR1) is reported to be associated with osteogenic differentiation. However, the underlying molecular mechanism remains elusive. Therefore, this study eval...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28100
更新日期:2018-12-16 00:00:00
abstract::Tumor cells display different bioenergetic profiles when compared to normal cells. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin A in breast cancer cells representing different stages of aggressiveness and metabolic profil...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.25036
更新日期:2015-05-01 00:00:00
abstract:OBJECTIVE:Hepatocellular carcinoma (HCC) has a high morbidity and mortality around the world, yet the effective therapeutic option for HCC is still limited. NPAC, also known as glyoxylate reductase 1 homolog, is a new nuclear protein recently implicated in tumor biology. However, the role of NPAC in HCC remains unclear...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28106
更新日期:2018-11-26 00:00:00
abstract::Receptor activator of nuclear factor kappa-B ligand (RANKL) is important substance during osteoclastogenesis that resulted in alveolar bone loss of periodontitis. MicroRNAs (miRNAs) regulate gene expression in several biological processes including osteoclastogenesis. We investigated the function of microRNA-302a-3p (...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.26456
更新日期:2018-06-01 00:00:00
abstract::We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.25735
更新日期:2017-03-01 00:00:00
abstract::Little is known about how adhesion molecules on APCs accumulate at immunological synapses. We show here that ICAM-1 on APCs is continuously internalized and rapidly recycled back to the interface after antigen-priming T-cell contact. The internalization rate is high in APCs, including Raji B cells and dendritic cells,...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.22798
更新日期:2010-12-01 00:00:00
abstract::Phospholipids, sphingolipids, and cholesterol are integral components of eukaryotic cell organelles, including the nucleus. Recent evidence shows characteristic features of nuclear lipid composition and signaling, which are distinct from that of the cytoplasm and plasma membrane. While the nuclear phosphoinositol lipi...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章,评审
doi:10.1002/jcb.26707
更新日期:2018-08-01 00:00:00
abstract::Lysophosphatidic acid (LPA) elicits diverse cellular responses through cell surface LPA receptors in nervous system-derived cells and cell lines. The developing nervous system is one of the major loci for LPA receptor expression. Recent studies have also revealed that metabolic pathways of LPA are present in the nervo...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章,评审
doi:10.1002/jcb.20093
更新日期:2004-08-01 00:00:00
abstract::Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs. Previous studies have suggested that BBR exerts antimicrobial, antitumor, and antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic gastritis. However, the exact mechanism by which BBR inhibits H. pylori infec...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.26681
更新日期:2018-07-01 00:00:00
abstract::Mechanical loading of bone generates fluid flow within the mineralized matrix that exerts fluid shear stress (FSS) on cells. We examined effects of FSS on receptor activator of nuclear factor kappa B ligand (RANKL), a critical factor for osteoclast formation. Primary murine osteoblasts were subjected to pulsatile FSS ...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.20864
更新日期:2006-08-01 00:00:00
abstract::A water soluble growth inhibitor was isolated from the mammalian ocular iris-ciliary complex. The molecular weight of this protein is 10 kD or lower as determined by ultrafiltration fractionation. The iris-ciliary (IC) complex water soluble protein(s) significantly inhibits synthesis of lower molecular weight proteins...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240500205
更新日期:1992-10-01 00:00:00
abstract::Muscle progenitor cells differentiate to myoblasts, and subsequently myotubes, upon expression of muscle specific genes. We and others have previously shown that myotube nuclei, even in the absence of nerve, express AChR alpha subunit RNA at varying levels, with a small subset (about ten percent) of the nuclei express...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.240580105
更新日期:1995-05-01 00:00:00
abstract::Relatively little information exists on the ultimate molecular mechanisms by which the lipogenic enzyme Fatty Acid Synthase (FAS) is differentially overexpressed in a biologically aggressive subset of human malignancies. Since the microenvironment of solid tumors contains regions of poor oxygenation and high acidity, ...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.20310
更新日期:2005-01-01 00:00:00
abstract::Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a number of tumorogenic or transformed cells, yet is relatively non-toxic to most normal cells, therefore, it is a promising agent for cancer therapy. However, some cancer cell lines were resistant to TRAIL cytoxicity, including...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.20535
更新日期:2005-10-15 00:00:00
abstract::Platelets are critical regulators of liver regeneration, but the mechanisms are still not fully understood. Platelets have been shown to contain a wide variety of microRNAs (miRNAs) and play an important role in many diseases. However, the mechanism that how the platelet microparticles (PMPs)-derived miRNA regulate th...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
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更新日期:2020-07-21 00:00:00
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pub_type: 杂志文章
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abstract::In women, calcium excretion in the urine rises after menopause and falls with estrogen replacement therapy. The amount of calcium lost in the urine following estrogen therapy is less than should occur based on changes in serum calcium and the amount of calcium filtered by the kidney. This suggests there may be a direc...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/(sici)1097-4644(19970601)65:3<340::aid-jcb
更新日期:1997-06-01 00:00:00
abstract::Choline-deficiency causes liver cells to die by apoptosis, and it has not been clear whether the effects of choline-deficiency are mediated by methyl-deficiency or by lack of choline moieties. SV40 immortalized CWSV-1 hepatocytes were cultivated in media that were choline-sufficient, choline-deficient, choline-deficie...
journal_title:Journal of cellular biochemistry
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doi:10.1002/(sici)1097-4644(199702)64:2<196::aid-jcb3>
更新日期:1997-02-01 00:00:00
abstract::CD4-positive helper T cells and CD8-positive cytotoxic T cells comprise the majority of T lymphocytes present in secondary lymphoid organs and are essential for acquired immunity. These two populations are derived from common precursors in the thymus and selected through interaction between their clonal T-cell recepto...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章,评审
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更新日期:2009-08-15 00:00:00
abstract:BACKGROUND:This study aimed to identify factors that affect the prognosis of budesonide therapy for Crohn's disease patients. METHOD:Change in Crohn's disease activity index (CDAI) scores at latest follow-up after budesonide therapy reported by individual studies were pooled to gain overall effect size under random ef...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章,meta分析
doi:10.1002/jcb.28310
更新日期:2019-06-01 00:00:00
abstract::Reduced insulin receptor protein levels have been reported in the kidney cortex from diabetic humans and animals. We recently reported that, targeted deletion of insulin receptor (IR) from proximal tubules (PT) resulted in hyperglycemia in non-obese mice. To elucidate the mechanism, we examined human proximal tubule c...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.25632
更新日期:2017-02-01 00:00:00
abstract::Roscovitine (ROSC), a selective cyclin-dependent kinase (CDK) inhibitor, arrests human estrogen receptor-α (ER-α) positive MCF-7 breast cancer cells in the G(2) phase of the cell cycle and concomitantly induces apoptosis via a p53-dependent pathway. The effect of ROSC is markedly diminished in MCF-7 cells maintained i...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.23004
更新日期:2011-03-01 00:00:00
abstract::CD19+ CD24hi CD38hi cells play an essential role in maintaining immune homeostasis. CD40 signaling is involved in regulating the induction and function of CD19+ CD24hi CD38hi cells. Changes in B-cell subpopulations and CD19+ CD24hi CD38hi cells have been observed in systemic lupus erythematosus (SLE) patients. Whether...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.28427
更新日期:2019-02-16 00:00:00
abstract::In addition to cholesterol-lowering effect, HMG-CoA reductase inhibition by statins has been shown to have protective effect in many cells type. The loss of vision in retinal degeneration disease associates with oxidative stress and apoptosis in retinal pigment epithelium (RPE) cell. This study was designed to examine...
journal_title:Journal of cellular biochemistry
pub_type: 杂志文章
doi:10.1002/jcb.23173
更新日期:2011-09-01 00:00:00