Delayed neuronal death in ischemic hippocampus involves stimulation of protein tyrosine phosphorylation

1996 ◽  
Vol 271 (4) ◽  
pp. C1085-C1097 ◽  
Author(s):  
T. Ohtsuki ◽  
M. Matsumoto ◽  
K. Kitagawa ◽  
T. Mabuchi ◽  
K. Mandai ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Kainic Acid ◽  
Neuronal Death ◽  
Tyrosine Kinases ◽  
Ischemia Reperfusion ◽  
Delayed Neuronal Death ◽  
Mongolian Gerbils ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Stimulation Of

Glutamate triggers neuronal degeneration after ischemia-reperfusion in the brain. However, the details of intracellular signal transduction that propagates cell death remain unknown. The present work investigated whether protein tyrosine phosphorylation mediates neuronal death in the ischemic brain. Transient forebrain ischemia for 5-10 min in Mongolian gerbils or intoxication with the glutamate analogue kainic acid (12 mg/kg) in Sprague-Dawley rats caused neuronal death selectively in the hippocampus 2-4 days or 1 day later, respectively. Under these conditions, 160-, 115-, 105-, 92-, and 85-kDa proteins showed a significant increase in tyrosyl residue phosphorylation selectively in the hippocampus 3-12 h after ischemia or 4-8 h after kainic acid-induced seizures. Tyrosine kinases, including pp60c-src, were activated without a change of tyrosine phosphatases. Administration of radicicol, a selective inhibitor of tyrosine kinases, attenuated stimulation of tyrosine phosphorylation and hippocampal degeneration after ischemia or kainic acid injection. The results suggest that protein tyrosine phosphorylation might propagate delayed neuronal death in the mature hippocampus through glutamate overload after ischemia-reperfusion.

Stimulation of protein-tyrosine phosphorylation by endothelin-1 in cultured vascular smooth muscle cells

1992 ◽  
Vol 92 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Masanobu Koide ◽  
Yasuhiro Kawahara ◽  
Terutaka Tsuda ◽  
Yoshihiro Ishida ◽  
Kozui Shii ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tyrosine Phosphorylation ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Endothelin 1 ◽  
Stimulation Of

scholarly journals The B cell antigen receptor of class IgD induces a stronger and more prolonged protein tyrosine phosphorylation than that of class IgM.

1995 ◽  
Vol 181 (3) ◽  
pp. 1005-1014 ◽  
Author(s):  
K M Kim ◽  
M Reth
Keyword(s):  
B Cell ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Antigen Receptor ◽  
Cross Linking ◽  
Protein Tyrosine Phosphorylation ◽  
Antigen Receptors ◽  
Antigen Specificity ◽  
Protein Tyrosine ◽  
Substrate Phosphorylation

Most mature B lymphocytes coexpress two classes of antigen receptor, immunoglobulin (Ig)M and IgD. The differences in the signal transduction from the two receptors are still a matter of controversy. We have analyzed B cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross-linking of these receptors with either antigen, or class-specific antibodies, results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetic and the intensity of phosphorylation, however, was quite different between the two receptors when they were cross-linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum after 1 minute and diminished after 60 minutes whereas, in the membrane IgD-expressing cells, the substrate phosphorylation increased further over time, reached its maximum at 60 minutes, and persisted longer than 240 minutes after exposure to antigen. As a result, the intensity of protein tyrosine phosphorylation induced by cross-linking of membrane IgD was stronger than that induced by membrane IgM. Studies of chimeric receptors demonstrate that only the membrane-proximal C domain and/or the transmembrane part of membrane-bound IgD molecule is required for the long-lasting substrate phosphorylation. Together, these data suggest that the signal emission from the two receptors is controlled differently.

Stimulation of protein tyrosine phosphorylation by platelet-activating factor and progesterone in human spermatozoa

1995 ◽  
Vol 108 (1-2) ◽  
pp. 35-42 ◽  
Author(s):  
Michaela Luconi ◽  
Lorella Bonaccorsi ◽  
Csilla Krausz ◽  
Ginetta Gervasi ◽  
Gianni Forti ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Platelet Activating Factor ◽  
Human Spermatozoa ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Stimulation Of

scholarly journals Constitutive secretion of serum albumin requires reversible protein tyrosine phosphorylation events in trans-Golgi

2005 ◽  
Vol 289 (3) ◽  
pp. C748-C756 ◽  
Author(s):  
Rachel J. Webb ◽  
Jacob D. Judah ◽  
Lee-Chiang Lo ◽  
Geraint M. H. Thomas
Keyword(s):  
Serum Albumin ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Protein Tyrosine Phosphorylation ◽  
Albumin Secretion ◽  
Protein Tyrosine ◽  
Constitutive Secretion

Serum albumin secretion from rat hepatocytes proceeds via the constitutive pathway. Although much is known about the role of protein tyrosine phosphorylation in regulated secretion, nothing is known about its function in the constitutive process. Here we show that albumin secretion is inhibited by the tyrosine kinase inhibitor genistein but relatively insensitive to subtype-selective inhibitors or treatments. Secretion is also blocked in a physiologically identical manner by the tyrosine phosphatase inhibitors pervanadate and bisperoxo(1,10-phenanthroline)-oxovanadate. Inhibition of either the kinase(s) or phosphatase(s) leads to the accumulation of albumin between the trans-Golgi and the plasma membrane, whereas the immediate precursor proalbumin builds up in a proximal compartment. The trans-Golgi marker TGN38 is rapidly dispersed under conditions that inhibit tyrosine phosphatase action, whereas the distribution of the cis-Golgi marker GM130 is insensitive to genistein or pervanadate. By using a specifically reactive biotinylation probe, we detected protein tyrosine phosphatases in highly purified rat liver Golgi membranes. These membranes also contain both endogenous tyrosine kinases and their substrates, indicating that enzymes and substrates for reversible tyrosine phosphorylation are normal membrane-resident components of this trafficking compartment. In the absence of perturbation of actin filaments and microtubules, we conclude that reversible protein tyrosine phosphorylation in the trans-Golgi network is essential for albumin secretion and propose that the constitutive secretion of albumin is in fact a regulated process.

scholarly journals IL-5 receptor-mediated tyrosine phosphorylation of SH2/SH3-containing proteins and activation of Bruton's tyrosine and Janus 2 kinases.

1994 ◽  
Vol 180 (6) ◽  
pp. 2101-2111 ◽  
Author(s):  
S Sato ◽  
T Katagiri ◽  
S Takaki ◽  
Y Kikuchi ◽  
Y Hitoshi ◽  
...  
Keyword(s):  
Signal Transduction ◽  
B Cell ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Catalytic Domain ◽  
Critical Role ◽  
Phosphatidyl Inositol ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Interleukin 5

Interleukin 5 (IL-5) induces proliferation and differentiation of B cells and eosinophils by interacting with its receptor (IL-5R) which consists of two distinct polypeptide chains, alpha and beta (beta c). Although both IL-5R alpha and beta c lack a kinase catalytic domain, IL-5 is capable of inducing tyrosine phosphorylation of cellular proteins. We investigated the role of IL-5R alpha in tyrosine phosphorylation of molecules involved in IL-5 signal transduction, using an IL-5-dependent early B cell line, Y16 and transfectants expressing intact or mutant IL-5R alpha together with intact beta c. The results revealed that the transfectants expressing truncated IL-5R alpha, which entirely lacks a cytoplasmic domain, together with beta c, showed neither protein-tyrosine phosphorylation nor proliferation in response to IL-5. This confirms that IL-5R alpha plays a critical role in protein-tyrosine phosphorylation which triggers cell growth. IL-5 stimulation results in rapid tyrosine phosphorylation of beta c and proteins containing Src homology 2 (SH2) and/or SH3 domains such as phosphatidyl-inositol-3 kinase, Shc, Vav, and HS1, suggesting their involvement in IL-5-mediated signal transduction. IL-5 stimulation significantly enhanced activities of Janus 2 and B cell-specific Bruton's tyrosine kinases (JAK2 and Btk) and increased the tyrosine phosphorylation of JAK2 kinase. These results and recent data on signaling of growth factors taken together, multiple biochemical pathways driven by tyrosine kinases such as JAK2 and Btk are involved in IL-5 signal transduction.

scholarly journals Protein tyrosine phosphorylation in rabbit peritoneal neutrophils

1990 ◽  
Vol 269 (2) ◽  
pp. 431-436 ◽  
Author(s):  
C K Huang ◽  
V Bonak ◽  
G R Laramee ◽  
J E Casnellie
Keyword(s):  
Tyrosine Phosphorylation ◽  
Kinase Inhibitor ◽  
Leukotriene B4 ◽  
Early Event ◽  
Ionophore A23187 ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Group A ◽  
Group B ◽  
Stimulation Of

Protein tyrosine phosphorylation in rabbit peritoneal neutrophils was examined by immunoblotting with antibodies specific for phosphotyrosine. Stimulation of the neutrophils with chemotactic factor fMet-Leu-Phe (10 nM) caused rapid increases of tyrosine phosphorylation of several proteins with apparent molecular masses of (Group A) 54-58 kDa and 100-125 kDa and (Group B) 36-41 kDa. Stimulation of Group A proteins was observed by fMet-Leu-Phe (10 nM, maximum at 20 s) and A23187 (1 microM, 1 min). Stimulation of Group B proteins was observed by fMet-Leu-Phe (ED50 0.15 nM, 1 min), leukotriene B4 (ED50 0.15 nM, 1 min), phorbol 12-myristate 13-acetate (PMA) (ED50 25 ng/ml, 10 min) and partially by ionophore A23187 (1 microM, 1 min). Pretreatment of the cell with the protein kinase inhibitor H-7 (25 microM, 5 min) and PMA (0.1 microgram/ml, 3 min) partially inhibited the fMet-Leu-Phe effect. However, pretreatment of the cells with quin 2/AM (20 microM, 10 min) completely inhibited the fMet-Leu-Phe effect. The results indicate that rapid regulation of tyrosine phosphorylation is an early event occurring in stimulated neutrophils. Furthermore the effect of fMet-Leu-Phe on tyrosine phosphorylation may require Ca2+ mobilization and may partially require the activity of H-7-sensitive protein kinases.

Protein tyrosine phosphorylation, cellular Ca2+, and Ca2+ sensitivity for contraction of smooth muscle

1994 ◽  
Vol 72 (11) ◽  
pp. 1434-1439 ◽  
Author(s):  
Joseph Di Salvo ◽  
Gabrielle Pfitzer ◽  
Lori A. Semenchuk
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Phosphorylation ◽  
Vascular Smooth Muscle Cells ◽  
Adrenergic Receptors ◽  
Kinase Activity ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Kinase Activity ◽  
Protein Tyrosine ◽  
Stimulation Of

Our studies are guided by the novel hypothesis that protein tyrosine phosphorylation is an important mechanism for regulating contraction of smooth muscle. Several lines of evidence are reviewed which suggest that enhanced tyrosine phosphorylation participates in mechanisms that regulate cytosolic Ca2+ and Ca2+ sensitivity for contraction. First, vanadate-induced contraction of guinea-pig taenia coli is functionally linked to enhanced protein tyrosine phosphorylation of at least three substrates, apparently resulting from vanadate-mediated inhibition of protein tyrosine phosphatase activity. Second, vanadate-induced contraction is dependent on extracellular Ca2+. Third, increases in cytosolic Ca2+ resulting from stimulation of αi-adrenergic receptors in cultured canine vascular smooth muscle cells are associated with enhanced tyrosine phosphorylation and are inhibited by genistein, a potent inhibitor of tyrosine kinase activity. Fourth, genistein markedly and reversibly suppresses Ca2+ sensitivity for contraction in ileal longitudinal smooth muscle permeabilized with staphylococcal α-toxin. Moreover, the same or similar substrates (e.g., 42–45, 70, 80–85, 95, 100, 110, 116, and 205 kDa) are tyrosine phosphorylated in response to Ca2+ or stimulation of muscarinic or αi-adrenergic receptors. Collectively, these data strongly suggest that tyrosine phosphorylation is an important mechanism for regulation of smooth muscle contraction.Key words: actin–myosin interaction, calcium sensitivity, genistein, permeabilized smooth muscle, tyrosine kinase activity, tyrosine phosphatase activity, vascular smooth muscle cells, vanadate.

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