Plasma membrane phosphatase

Consideration of membrane as a target for chemotherapeutic drugs has been reviewed and relevant studies with cisplatin summarized [79]. The amino acid uptake mechanism in LI 210 cells is affected by cisplatin [80] and platinum complexes inhibit plasma membrane phosphatase activity in ascites cells [81]. Microtubule protein polymerization is also affected adversely [82]. Effects on mitochondrial functions and properties have been examined [83—86], along with studies on inhibition of sulfhydryl-containing enzymes [87—90]. 

The secretory vesicles have recently been discovered by Borregaard and co-workers (Sengelpv, Nielson Borregaard, 1992). These are very difficult to separate from the plasma membrane on density gradients. They possess latent alkaline phosphatase activity (i.e. subcellular fractions must be incubated with detergents such as Triton to release activity) and albumin, whilst the membranes contain CR1, CR3 and the fMet-Leu-Phe receptor. They are endocytic vesicles but can be rapidly translocated to the plasma membrane. 

Sengelpv, H., Nielson, M. H., Borregaard, N. (1992). Separation of human neutrophil plasma membrane from vesicles containing alkaline phosphatase and NADPH oxidase activity by free flow electrophoresis. J. Biol. Chem. 267,14912-17. 

Fig. 3. Intracellular transport route of the SFV spike glycoproteins from the endoplasmic reticulum (ER), over the Golgi apparatus, to the plasma membrane (PM). The cis cisternae do not react positively for add phosphatase or thiamin pyrophosphatase, and do not label with ridn in thin frozen sections. The medial cisternae do not react positively for thiamin pyrophosphatase or acid phosphatase, but label with ridn. The trans cisternae are positive for all of these markers.

Enzyme Ei is the phospholipase A, for which there is an excess of substrate in the plasma membrane i.e. a zero order process. (Eor details of this process, see Chapter 11). E, is a phosphatase, which catalyses a first order process. In fact, IP2 can be hydrolysed to produce IPi which is further hydrolysed to produce free inositol. The latter is salvaged by using it to re-form phosphatidylinositol in the phospholipid synthetic pathway and then phosphorylated to prodnce PIP2 (Chapter 11, Eigure 11.21). These reactions are not jnst of biochemical interest bnt are involved in the treatment of bipolar disease a mental disorder. 

Transporters in the plasma membrane of hepatocytes allow insulin-independent transport of glucose and other sugars in both directions. In contrast to muscle, the liver possesses the enzyme glucose-6-phosphatase, which can release glucose from glucose-6-phosphate. 

For the 3 adrenoceptor, and many other serpentine receptors, 3-arrestin binding also accelerates endocytosis of receptors from the plasma membrane. Endocytosis of receptors promotes their dephosphorylation, by a receptor phosphatase that is present at high concentration on endosome membranes, and receptors then return to the plasma membrane. This helps explain the ability of cells to recover receptor-mediated signaling responsiveness very efficiently after agonist-induced desensitization. 

In another approach subcellular fractionation of human PMNs, stimulated in vitro with phorbol myristate acetate or opsonized zymsan, was performed by rate-zonal centrifugation in sucrose gradients By varying the centrifugal force the NADPH oxidase could be separated from the activities of enzymes in the lysosomal granules but was similar to the distribution of markers for the plasma membrane, aryl phosphatase, alkaline phosphodiesterase I, and acid aryl phosphatase. 

In addition to the many receptors that act as protein Tyr kinases, a number of receptorlike plasma membrane proteins have protein Tyr phosphatase activity. Based on the structures of these proteins, we can surmise that their ligands are components of the extracellular matrix or the... 

Proteins with long C-terminal hydrophobic signal sequences may become attached to phosphatidylinositol-glycan anchors embedded in the plasma membrane (Fig. 8-13). An example is a human alkaline phosphatase in which the a carboxyl of the terminal aspartate residue forms an amide linkage with the ethanolamine part of the anchor. Attachment may occur by a direct attack of the -NH2 group of the ethanolanine on a peptide linkage in a transacylation reaction that releases a 29-residue peptide from the C terminus.118119 (See Chapter 29). 

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