Human stomatin (band 7.2b) is a 31-kDa erythrocyte membrane protein of unknown function but implicated in the control of ion channel permeability, mechanoreception, and lipid domain organization. Although absent in erythrocytes from patients with hereditary stomatocytosis, stomatin is not linked to this disorder. A second stomatin homologue, termed SLP-1, has been identified in nonerythroid tissues, and other stomatin related proteins are found in Drosophila, Caenorhabditis elegans, and plants. We now report the cloning and characterization of a new and unusual stomatin homologue, human SLP-2 (stomatin-like protein 2). SLP-2 is encoded by an ϳ1.5-kilobase mRNA (GenBank TM accession no. AF190167). The gene for human SLP-2, HUSLP2, is present on chromosome 9p13. Its derived amino acid sequence predicts a 38,537-kDa protein that is overall ϳ20% similar to human stomatin. Northern and Western blots for SLP-1 and SLP-2 reveal a wide but incompletely overlapping tissue distribution. Unlike SLP-1, SLP-2 is also present in mature human erythrocytes (ϳ4,000 ؎ 5,600 (؎ 2 S.D.) copies/cell). SLP-2 lacks a characteristic NH 2 -terminal hydrophobic domain found in other stomatin homologues and (unlike stomatin) is fully extractable from erythrocyte membranes by NaOH, pH 11. SLP-2 partitions into both Triton X-100-soluble and -insoluble pools in erythrocyte ghost membranes or when expressed in cultured COS cells and migrates anomalously on SDS-polyacrylamide gel electrophoresis analysis with apparent mobilities of ϳ45,500, 44,600, and 34,300 M r . The smallest of these protein bands is believed to represent the product of alternative translation initiated at AUGs beginning with nt 217 or 391, although this point has not been rigorously proven. Collectively, these findings identify a novel and unusual member of the stomatin gene superfamily that interacts with the peripheral erythrocyte cytoskeleton and presumably other integral membrane proteins but not directly with the membrane bilayer. We hypothesize that SLP-2 may link stomatin or other integral membrane proteins to the peripheral cytoskeleton and thereby play a role in regulating ion channel conductances or the organization of sphingolipid and cholesterol-rich lipid rafts.Previously known as band 7.2b because of its relative electrophoretic mobility in samples of human red blood cell ghost preparations, stomatin is a less characterized integral erythrocyte membrane protein with a molecular mass of 31 kDa (1, 2). Deficiency of stomatin in red cells is associated with hereditary stomatocytosis, a disease with marked red cell shape abnormalities and increased monovalent cation permeability (for reviews, see Refs. 3 and 4). However, linkage studies and direct sequencing establish that a defect in stomatin is not the cause of this disorder (4 -6), and mice lacking stomatin retain normal red cell morphology and apparently normal function (7). The role of stomatin thus remains a mystery. In a human amniotic cell line, stomatin concentrates preferentially in plasma membrane prot...

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Using the efficient discrete-ordinate method, we present an analytical solution for radiative transfer in the coupled atmosphere-ocean system with rough air-water interface.The theoretical formulations of the radiative transfer equation and solution are described.The effects of surface roughness on radiation field in the atmosphere and ocean are studied and compared with measurements. The results show that ocean surface roughness has significant effects on the upwelling radiation in the atmosphere and the downwelling radiation in the ocean. As wind speed increases, the angular domain of sunglint broadens, the surface albedo decreases, and the transmission to ocean increases. The downward radiance field in the upper ocean is highly anisotropic, but this anisotropy decreases rapidly as surface wind increases and as depth in ocean increases. The effects of surface roughness on radiation also depend greatly on both wavelength and angle of incidence (i.e., solar elevation); these effects are significantly smaller throughout the spectrum at high sun. The model-observation discrepancies may indicate that the Cox-Munk surface roughness model is not sufficient for high wind conditions.

SHP-1 has been proposed to be a tumor suppressor gene for several cancers. The expression of SHP-1 protein is diminished or abolished in most leukemia and lymphoma cell lines and tissues, and in some non-hematopoietic cancer cell lines, such as estrogen receptor (ER) negative breast cancer cell lines and some colorectal cancer cell lines. However, we do not know whether the reduced SHP-1 expression is the cause of cancer diseases or the secondary effect of cancer developments. Here, we first demonstrate that SHP-1 has general tumor suppressing function in SHP-1 transfected cell lines. Transfected SHP-1 inhibits the growth of three lymphoma/leukemia cell lines (Ramos, H9, Jurkat) and one breast cancer cell line (HTB26). We also demonstrate a possible molecular mechanism for the tumor suppressing function of SHP-1: SHP-1 inhibits cell growth partly by negative regulation of activated JAK kinase. In addition, we find, for the first time, that SHP-1 down-regulates the level of TYK2 kinase in H9 cells and of JAK1 kinase in HTB26 cells, by accelerating their degradation. The SHP-1 accelerated degradation of JAK1 kinase in HTB26 cells was blocked with the treatment of MG132, a specific inhibitor for proteasome-mediated proteolysis. Our data suggest a new function of SHP-1 in the regulation of proteasome-mediated degradation pathway.

Ecto-5¢-nucleotidase (CD73), a cell surface protein that hydrolyzes extracellular AMP into adenosine and phosphate, is overexpressed in many solid tumors. In this study, we tested the hypothesis that increased CD73 may promote tumor progression by examining the effect of CD73 suppression via RNA interference and CD73 overexpression on tumor growth in vivo and in vitro. Using digitized whole-body images, plate clone forming assay and TUNEL assay in frozen tissue sections, we found that the cell growth rate was significantly lower in vivo and in vitro after CD73 suppression and late apoptosis was much higher in xenograft tumors developed from the CD73-siRNA transfected MB-MDA-231 clone (P1). By flow cytometry, the P1 cell cycle was arrested in the G0/G1 phase. Moreover, Bcl-2 was downregulated, while Bax and caspase-3 were upregulated with CD73 suppression. CD73 inhibitor a,b-methylene adenosine-5¢-disphosphate (APCP) functioned similarly with RNAimediated CD73 suppression. In addition, in transfected MCF-7 cells, we found that CD73 overexpression increased cell viability and promoted cell cycle progression, depending on its enzyme activity. More intriguingly, CD73 overexpression in MCF-7 breast cancer cells produces a tumorigenic phenotype. We conclude that CD73 plays an important role in breast cancer growth by affecting cell cycle progression and apoptosis. (Cancer Sci 2010; 101: 2561-2569 B reast cancer develops in 14% of women and is a leading cause of cancer death in women around the world.(1)Understanding the molecular mechanisms of breast carcinoma progression is important for effective treatments. Ecto-5¢-nucleotidase (CD73) is a 70 kDa glycosylated protein that is bound to the outer surface of the plasma membrane by a glycosyl phosphatidyl inositol anchor and co-localized with detergent-resistant and glycolipid-rich membrane sub-domains called lipid rafts.(2) CD73 hydrolyzes extracellular AMP into adenosine and phosphate. Adenosine, a proliferative factor, acting through Gprotein coupled receptors, produces a spectrum of physiological functions.(3) In addition, it causes tumor growth, angiogenesis and immune suppression.(4) CD73 upregulation is associated with a highly invasive cancer phenotype, drug resistance and tumor-promoting functions.(5) In addition to acting as a hydrolytic enzyme to generate adenosine, CD73 may serve as an adhesive molecule and interact with extracellular matrix glycoprotein, such as fibronectin and laminin, to produce cancer-invasive properties.(6) Bavaresco et al. (7) reported that CD73 mediated glioma cell proliferation depends upon adenosine. Furthermore, CD73 is overexpressed in the progression of many human solid tumors, such as breast cancer, (8,9) papillary thyroid carcinomas, (10) melanoma (11) and prostate cancer. (12) All these factors implicate the crucial role of CD73 in tumorigenesis. To date, our knowledge on the mechanisms of CD73 on tumor growth is still limited. Previously, we showed that CD73 may promote metastasis by facilitating the migration, adhesion and i...

Angiogenesis is essential for tumor growth, progression and metastasis. Studies indicate that expression and activity of ecto-5'-nucleotidase (CD73) are elevated in metastatic carcinomas. Our previous studies found that angiogenesis of tumor xenografts was decreased when the activity of CD73 in cancer cells was inhibited, implying that this enzyme is involved in tumor angiogenesis. To elucidate the mechanism, we investigated CD73 influence on tumor angiogenesis in both in vitro assays and in tumor bearing mice. We found that capillary-like structures were formed more in CD73(+/+) pulmonary microvascular endothelial cells (PMECs) than CD73(-/-) PMECs, and this was more pronounced when the cells were cultured in cancer-conditioned medium. Meanwhile, CD73 decreased endothelial cells adhesion to collagen IV and promoted migration. Additionally, the extent of tumor angiogenesis and the size of tumors were greater in CD73(+/+) mice than in CD73(-/-) mice. Thus, we concluded that CD73 can promote endothelial cells forming new vessels in cancer condition, facilitating tumor growth and hematogenous metastasis.

A simple yet accurate parameterization of spectral and broadband ocean surface albedo has been developed. To facilitate the parameterization and its applications, the albedo is parameterized for the direct and diffuse incident radiation separately, and then each of them is further divided into two components: the contributions from surface and water, respectively. The four albedo components are independent of each other, hence, altering one will not affect the others. Such a designed parameterization scheme is flexible for any future update. Users can simply replace any of the adopted empirical formulations (e.g., the relationship between foam reflectance and wind speed) as desired without a need to change the parameterization scheme. The parameterization is validated by in situ measurements and can be easily implemented into a climate or radiative transfer model.