Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spectrin Rouen (beta 220/218) is a novel variant, carrying a shortened beta chain with an apparent molecular weight of 218 kDa. It was detected in a French family. All affected members suffered from haemolytic hereditary elliptocytosis. As other shortened beta chain variants described before, the beta Rouen chain is truncated at its carboxyl terminus. Spectrin Rouen is associated with a defect in spectrin dimer self-association and with an abnormally high amount of the alpha I 74 kDa peptide following partial tryptic digestion. Dimer reconstitution experiments from normal and abnormal purified Sp subunits indicated that the increased alpha I 74 kDa fragment is induced by the altered beta chain. However, spectrin Rouen is different from other mutants with a truncated beta chain in several respects: its amount is low (less than 10%) and the spectrin dimer self-associated defect is mild. Critically, the beta Rouen chain has retained the ability of undergoing phosphorylation, even though it is modified in its C-terminal region. These results, compared to those obtained with beta 220/214 spectrin Le Puy and beta 220/216 spectrin Nice, allowed better localization of the beta chain sites that can be phosphorylated by a membrane-bound casein kinase.
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PMID:Elliptocytosis-associated spectrin Rouen (beta 220/218) has a truncated but still phosphorylatable beta chain. 155 Jul 83

As yet there is no single test specific for the diagnosis of hereditary spherocytosis. In the search for a specific test, a method described by Pinder et al. [14] using a cAMP-independent protein kinase extracted from normal erythrocyte membranes was used. Membrane skeletons were prepared from erythrocyte ghosts by extraction with a non-ionic detergent, i.e., Triton X-100. Upon phosphorylation with c-AMP-independent protein kinase the suspension of normal membrane skeletons set to a gelatinous mass. Membrane skeletons from patients with spherocytosis failed to show this phenomenon. In order to clarify whether this phenomenological difference can be used as a diagnostic tool for hereditary spherocytosis, a semiquantitative method of observing the gelation process was used under definite shear stress conditions. We investigated 33 patients with different hemolytic anemias (spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis, homozygous beta-thalassemia and enzymopenic hemolytic anemias). With the exception of spherocytosis, all preparations of membrane skeletons showed gelation after 30-50 min. Spherocytosis membrane skeletons did not show a significant gelation even after 12 h of incubation. Thus, the failing gelation is specific for the diagnosis of hereditary spherocytosis. The "gelation assay" might be a valuable method for defining patients with hemolytic anemias due to erythrocyte membrane defects. Its molecular basis and the possible importance for the pathogenesis of spherocytosis require further investigations.
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PMID:Absence of phosphorylation-induced gelation of erythrocyte membrane skeletons: a diagnostic tool for hereditary spherocytosis. 155 1

In four members of a family presenting hereditary elliptocytosis erythrocytes were studied, membranes were extracted and proteins were analysed by gel electrophoresis in a polyacrylamide gradient. In one of the patients suffering from severe haemolytic anaemia successfully treated by splenectomy, an almost complete deficiency in band 4(1) was discovered. Endogenous protein kinase activities revealed the absence of radioactivity of band 4(1) in the proband, a result not modified by cAMP. The kinase activity was normal in the parents, which confirms the almost complete absence of protein 4(1) seen in the stained gel of the proband. A moderate increase in the phosphorylation of band 3 was observed in all the members of this family. Deformability was measured by a visco-diffractometric method (Ektacytometry) in a medium of low viscosity (11 cp at 22 degrees C), allowing the recording of curves characteristic of elliptocytosis and revealing a markedly reduced deformability index (DI). At low shear stress, elliptocytes were oriented perpendicular to the flow (a result common to all elliptocytosis). In the proband several years after splenectomy, the DI was extremely reduced at high shear stress, which can be explained by the simultaneous presence of elliptocytes, schizocytes and spherocytes. A more detailed comparative study of the proteins of the various members of the family could lead to more precise information on the possible role of band 4(1) as a linkage protein maintaining the erythrocyte membrane stability.
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PMID:[1st instance of the absence of an erythrocyte membrane protein (band 4(1)) in a case of familial elliptocytic anemia]. 725 53

The composition of the erythrocyte plasma membrane is extensively modified during the intracellular growth of the malaria parasite Plasmodium falciparum. It has been previously shown that an 80-kD phosphoprotein is associated with the plasma membrane of human red blood cells (RBCs) infected with trophozoite/schizont stage malaria parasites. However, the identity of this 80-kD phosphoprotein is controversial. One line of evidence suggests that this protein is a phosphorylated form of RBC protein 4.1 and that it forms a tight complex with the mature parasite-infected erythrocyte surface antigen. In contrast, evidence from another group indicates that the 80-kD protein is derived from the intracellular malaria parasite. To resolve whether the 80-kD protein is indeed RBC protein 4.1, we made use of RBCs obtained from a patient with homozygous 4.1(-) negative hereditary elliptocytosis. RBCs from this patient are completely devoid of protein 4.1. We report here that this lack of protein 4.1 is correlated with the absence of phosphorylation of the 80-kD protein in parasite-infected RBCs, a finding that provides conclusive evidence that the 80-kD phosphoprotein is indeed protein 4.1. In addition, we also identify and partially characterize a casein kinase that phosphorylates protein 4.1 in P falciparum-infected human RBCs. Based on these results, we suggest that the maturation of malaria parasites in human RBCs is accompanied by the phosphorylation of protein 4.1. This phosphorylation of RBC protein 4.1 may provide a mechanism by which the intracellular malaria parasite alters the mechanical properties of the host plasma membrane and modulates parasite growth and survival in vivo.
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PMID:Phosphorylation of protein 4.1 in Plasmodium falciparum-infected human red blood cells. 819 70