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.

Inhibition by 5′-methylthioadenosine of cell growth and tyrosine kinase activity stimulated by fibroblast growth factor receptor in human gliomas

1995 ◽  
Vol 83 (4) ◽  
pp. 690-697 ◽  
Author(s):  
Katsuya Miyaji ◽  
Eiichi Tani ◽  
Atsuhisa Nakano ◽  
Hideyasu Ikemoto ◽  
Keizo Kaba
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Glioma Cells ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Kinase Activity ◽  
Protein Tyrosine

✓ Stimulation of three human glioma cell lines with basic fibroblast growth factor (bFGF) led to the enhancement of cell growth and the rapid tyrosine phosphorylation of cellular proteins, including major substrates of 90 kD. A methyltransferase inhibitor, 5′-methylthioadenosine (MTA), inhibited dose dependently the bFGF-stimulated cell growth and protein tyrosine phosphorylation in glioma cells by blocking both receptor autophosphorylation and substrate phosphorylation, as shown by immunoblotting with antiphosphotyrosine antibodies and cross-linking bFGF to receptors. The antiproliferative activity of MTA correlated quantitatively with its potency as an inhibitor of bFGF-stimulated protein tyrosine kinase activity. The methyltransferase inhibitor MTA had no effect on either epidermal growth factor— or platelet-derived growth factor—stimulated protein tyrosine phosphorylation in glioma cells, but inhibited specifically bFGF-stimulated protein tyrosine kinase activity. The concentration of MTA required for inhibition of protein methylation correlated well with the concentration required for inhibition of bFGF-stimulated cell growth and protein tyrosine phosphorylation. Because MTA had no effect on numbers and dissociation constants of high- and low-affinity bFGF receptors, the inhibition of bFGF-stimulated bFGF receptor tyrosine kinase activity is not likely to be the result of a reduction in bFGF receptor and bFGF binding capacity. In fact, MTA delayed and reduced the internalization and nuclear translocation of bFGF, and the internalized bFGF was submitted to a limited proteolysis that converted it to lower molecular peptides whose presence remained for at least 22 hours. The effect of MTA on bFGF-stimulated tyrosine phosphorylation was immediate and readily reversible.

scholarly journals Tissue-dependent regulation of protein tyrosine kinase activity during embryonic development.

1991 ◽  
Vol 112 (5) ◽  
pp. 955-963 ◽  
Author(s):  
P A Maher
Keyword(s):  
Embryonic Development ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Kinase Activity ◽  
Protein Tyrosine ◽  
Low Levels ◽  
Protein Tyrosine Kinase Activity

Protein tyrosine kinase activity was assayed in a variety of chicken tissues during embryonic development and in the adult. In some tissues protein tyrosine kinase activity decreased during embryonic development; however, in other tissues it remained high throughout development, it contrast to the level of protein tyrosine phosphorylation, which decreased during development. The highest levels of tyrosine kinase activity were detected in 17-d embryonic brain although only low levels of protein tyrosine phosphorylation were observed in this tissue. Several alternatives were examined in an effort to determine the mechanism responsible for the low levels of tyrosine phosphorylated proteins in most older embryonic and adult chicken tissues despite the presence of highly active tyrosine kinases. The results show that the regulation of protein tyrosine phosphorylation during embryonic development is complex and varies from tissue to tissue. Furthermore, the results suggest that protein tyrosine phosphatases play an important role in regulating the level of phosphotyrosine in proteins of many older embryonic and adult tissues.

scholarly journals Vasoconstrictor-induced protein-tyrosine phosphorylation in cultured vascular smooth muscle cells

FEBS Letters ◽  
1991 ◽  
Vol 285 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Terutaka Tsuda ◽  
Yasuhiro Kawahara ◽  
Kozui Shii ◽  
Masanobu Koide ◽  
Yoshihiro Ishida ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tyrosine Phosphorylation ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

scholarly journals Haemin enhancement of glucose transport in human lymphocytes: stimulation of protein tyrosine phosphatase and activation of p56lck tyrosine kinase

1993 ◽  
Vol 291 (1) ◽  
pp. 281-287 ◽  
Author(s):  
H M Lander ◽  
D M Levine ◽  
A Novogrodsky
Keyword(s):  
Tyrosine Kinase ◽  
Glucose Uptake ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Human Lymphocytes ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Ptpase Activity ◽  
Stimulation Of

Following our previous observation that haemin is mitogenic for human lymphocytes, we investigated the ability of haemin to enhance glucose uptake in these cells. We found that preincubation of human peripheral-blood mononuclear cells (PBMC) with haemin for 60 min increased up to 5-fold the rate of 2-deoxy-D-[1-3H]glucose uptake by the cells. Actinomycin D and cycloheximide did not inhibit the effect, and cytochalasin B completely blocked it. Among the metalloporphyrins tested (Fe-, Ni-, Co-, Zn- and Sn-protoporphyrin), only haemin (Fe-protoporphyrin) induced a marked increase in glucose uptake. Thiourea, a scavenger of oxygen free radicals, and 3-amino-1,2,4-triazole inhibited haemin-induced glucose uptake. Oxidants such as H2O2 and phenylarsine oxide were previously reported to stimulate protein tyrosine phosphorylation and to enhance glucose uptake. We found that incubation of PBMC with haemin resulted in an increase in protein tyrosine phosphatase (PTPase) activity, probably that identified as CD45. Similarly to haemin, we found that phytohaemagglutinin also enhanced PTPase activity. Haemin also activated the tyrosine kinase p56lck, which is negatively controlled by phosphorylation of Tyr-505 at the C-terminus, and increased protein tyrosine phosphorylation in these cells. Tyrphostins, specific inhibitors of tyrosine kinases, at low concentrations markedly enhanced glucose uptake and synergized with haemin in enhancing glucose uptake. At high doses, tyrphostins inhibited the effect of haemin. Taken together, we postulate that haemin enhancement of glucose uptake in human lymphocytes results from its stimulation of PTPase, followed by activation of tyrosine kinase p56lck, leading to an increase in protein tyrosine phosphorylation.

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