Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein.

Lowe, Mark E.

doi:10.1083/jcb.116.3.799

Cited by 45 publications

(24 citation statements)

References 23 publications

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“…Substitution of Arg304 by Leu restored the correct glycosyl-PtdIns linkage, suggesting that the presence of a positively charged residue damages a potentially functional glycosyl-PtdIns signal. This is in agreement with proposals based on recent studies on other glycosylPtdIns proteins (Berger et al, 1988;Nuoffer et al, 1991;Lowe, 1992). The present finding that substitution of Arg304 by Glu led to only partial restoration of glycosyl-Ptdlns anchoring, demonstrates, however, that acid residues can also interfere negatively with glycosyl-PtdIns anchoring, although not as drastically as basic residues.…”

Section: Discussionsupporting

confidence: 80%

“…However, the u-PAR variants, despite their intracellular localization, did have binding activity. Aberrant variants of other glycosyl-PtdIns proteins have been observed intracellularly (Moran et al, 1991), secreted in the culture medium (Nuoffer et al, 1991 ;Lowe, 1992) or even in the form of transmembrane polypeptide structures (Waneck et al, 1988). In the case of u-PAR, the results obtained are intriguing, since successful secretion has been obtained by truncation of the last 33 amino acid residues , i.e.…”

Section: Discussionmentioning

confidence: 71%

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Structural requirements for glycosyl‐phosphatidylinositol‐anchor attachment in the cellular receptor for urokinase plasminogen activator

Møller

Ploug

Blasi

1992

European Journal of Biochemistry

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The urokinase-plasminogen-activator receptor (u-PAK) is a glycosyl-phosphatidylinositol(g1y-cosyl-Ptd1ns)-anchored membrane protein. Using site-directed mutagenesis, we have studied features in the u-PAR sequence important for successful glycosyl-PtdIns attachment. Two critical sequence elements were identified. In the sequence Ser282-Gly283-Ala284, simultaneous substitution of all of these residues prevented membrane anchoring. Individual substitution of each of the residues indicated that Gly283 is the more critical residue and the likely attachment site. However, it was unexpectedly found that mutation of this residue gave rise only to a partial impairment of glycosyl-PtdIns attachment. We therefore propose that more than one residue within this sequence can be utilized as glycosyl-PtdIns-attachment site. In the last eight COOH-terminal amino acids encoded in u-PAR cDNA, deletion of this sequence (residues 306 -31 3) completely prevented glycosyl-PtdIns attachment. However, the remaining COOH-terminal region proved still to possess a potential glycosylPtdIns signal activity; it could be converted to a new functional glycosyl-PtdIns signal by substitution of a single positively charged residue (Arg304). Substitution of Arg304 by Leu converted this truntaced u-PAR to a glycosyl-PtdTns-anchored protein. indistinguishable from the wild type. Substitution of Arg304 by a negatively charged residue (Glu) led to a partial aquisition of the glycosyl-PtdInsanchoring ability. These findings show that charged amino acids placed in the COOH-terminus interfere negatively with glycosyl-Ptdlns-anchoring, and, furthermore, that this effect is more pronounced for positively charged than for negatively charged amino acid residues.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 71%

Structural requirements for glycosyl‐phosphatidylinositol‐anchor attachment in the cellular receptor for urokinase plasminogen activator

Møller

Ploug

Blasi

1992

European Journal of Biochemistry

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“…Otherwise, proteins are retained in the ER in an inactive conformation [555]. Conversely, interruption of the C-terminal 29-amino acid hydrophobic stretch by a charged residue resulted in protein secretion into the medium [557]. Processing of PLAP can also be demonstrated in cell-free systems [558].…”

Section: Glycosylationmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

888

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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“…Immunofluorescence was done as previously described except that the secondary antibody was a FITC-anti-rabbit IgG and the hydrogen peroxide wash was eliminated (26). The FITC-anti-rabbit IgG was incubated on the tissue sections in PBS-T (137 mM NaCl, 2.7 mM KCl, 4.3 928 mM Na 2 HPO 4 ·H 2 O, 1.4 mM KH 2 PO 4 , 0.2% Tween-20) for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Expression of a Novel Cadherin in the Mouse and Human Intestine

Moulton¹,

Crandall²,

Lakhani³

et al. 2004

Pediatr Res

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Members of the cadherin superfamily mediate critical interactions in tissue differentiation and organogenesis, including differentiation and maintenance of the intestine. In this study, we report the identification and expression of a novel cadherin in the intestinal epithelium. We identified this cDNA by subtraction hybridization and obtained subsequent clones by screening a human cDNA library. Tissue distribution of the mRNA encoding the cadherin was assessed by RNA blot, reverse transcriptase PCR, and in situ hybridization. Protein expression was analyzed by protein blot and immunohistochemistry. The cDNA encodes an integral membrane protein with four consecutive cadherin binding domains followed by a series of mucin domains, a unique feature of this cadherin. Differences in the mucin domains account for four splice-forms. Multiple potential SH3-binding domains and a single potential PDZ-binding domain follow the transmembrane domain. Analysis revealed expression in the liver, kidney, and intestine. Three splice variants were found in the embryonic intestine as early as embryonic d 13 and in the adult intestine. The mRNA localizes to the mature enterocytes throughout the mouse small intestine and the protein, including several species from 90 to 100 kD, resides on the enterocyte basolateral membrane. We have identified intestinal expression of a novel cell cadherin with features suggesting the potential to transduce signals from neighboring cells to the cytoplasm. The intestinal epithelium undergoes a rapid and continuous process of cellular renewal involving cell turnover and regeneration (1, 2). Cell turnover entails a sequence of cell proliferation, differentiation, migration, and programmed cell death. Pluripotential epithelial stem cells reside near the base of each crypt of Lieberkuhn and provide a continuous supply of mature epithelial cells. Daughter cells that arise from these stem cells proliferate rapidly and differentiate during a bipolar migration into one of four principle epithelial cell lineages. As a result, enterocytes, goblet cells, and enteroendocrine cells populate the villus epithelium whereas Paneth cells reside at the base of the crypts along with stem cells (3, 4). Cell lineages undergo differentiation as they migrate up the epithelial villus. After 3-5 d, cells on the villous tip are shed through a process involving apoptosis (5-7). Consequently, development and maintenance of normal intestinal epithelial morphology requires tight regulatory control of cell proliferation, migration, and differentiation along the crypt-villus axis.The coordination of these processes in building the normal architecture of the intestinal epithelium depends on selective interactions of the cells with other cells and with the extracellular matrix (8, 9). Multiple molecules have been identified that mediate intercellular and cell-to-matrix adhesive functions (10 -12). Most belong to one of a few supergene families, the selectin, the immunoglobulin, the integrin, or the cadherin families. Members of the int...

show abstract

Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein.

Cited by 45 publications

References 23 publications

Structural requirements for glycosyl‐phosphatidylinositol‐anchor attachment in the cellular receptor for urokinase plasminogen activator

Structural requirements for glycosyl‐phosphatidylinositol‐anchor attachment in the cellular receptor for urokinase plasminogen activator

Cellular function and molecular structure of ecto-nucleotidases

Expression of a Novel Cadherin in the Mouse and Human Intestine

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