ASSOCIATION OF THE PROTEIN TYROSINE PHOSPHATASE CD45 WITH THE PROTEIN TYROSINE KINASE LCK AND THE ADAPTER PROTEIN LAT

2000 ◽  
Vol 28 (5) ◽  
pp. A428-A428
Author(s):  
Stuart D. Edmonds ◽  
Hanne L. Ostergaard
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Protein Tyrosine Kinase ◽  
Tyrosine Phosphatase ◽  
Adapter Protein ◽  
Protein Tyrosine

Effects of protein tyrosine kinase and protein tyrosine phosphatase on apical K+ channels in the TAL

2001 ◽  
Vol 281 (4) ◽  
pp. C1188-C1195 ◽  
Author(s):  
Rui-Min Gu ◽  
Yuan Wei ◽  
John R. Falck ◽  
U. Murali Krishna ◽  
Wen-Hui Wang
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Protein Tyrosine Kinase ◽  
Tyrosine Phosphatase ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Patch Clamp Technique ◽  
K Channels ◽  
Protein Tyrosine ◽  
Herbimycin A

We have previously demonstrated that the protein level of c-Src, a nonreceptor type of protein tyrosine kinase (PTK), was higher in the renal medulla from rats on a K-deficient (KD) diet than that in rats on a high-K (HK) diet (Wang WH, Lerea KM, Chan M, and Giebisch G. Am J Physiol Renal Physiol 278: F165–F171, 2000). We have now used the patch-clamp technique to investigate the role of PTK in regulating the apical K channels in the medullary thick ascending limb (mTAL) of the rat kidney. Inhibition of PTK with herbimycin A increased NP o, a product of channel number ( N) and open probability ( P o), of the 70-pS K channel from 0.12 to 0.42 in the mTAL only from rats on a KD diet but had no significant effect in tubules from animals on a HK diet. In contrast, herbimycin A did not affect the activity of the 30-pS K channel in the mTAL from rats on a KD diet. Moreover, addition of N-methylsulfonyl-12,12-dibromododec-11-enamide, an agent that inhibits the cytochrome P-450-dependent production of 20-hydroxyeicosatetraenoic acid, further increased NP o of the 70-pS K channel in the presence of herbimycin A. Furthermore, Western blot detected the presence of PTP-1D, a membrane-associated protein tyrosine phosphatase (PTP), in the renal outer medulla. Inhibition of PTP with phenylarsine oxide (PAO) decreased NP o of the 70-pS K channel in the mTAL from rats on a HK diet. However, PAO did not inhibit the activity of the 30-pS K channel in the mTAL. The effect of PAO on the 70-pS K channel was due to indirectly stimulating PTK because pretreatment of the mTAL with herbimycin A abolished the inhibitory effect of PAO. Finally, addition of exogenous c-Src reversibly blocked the activity of the 70-pS K channel in inside-out patches. We conclude that PTK and PTP have no effect on the low-conductance K channels in the mTAL and that PTK-induced tyrosine phosphorylation inhibits, whereas PTP-induced tyrosine dephosphorylation stimulates, the apical 70-pS K channel in the mTAL.

scholarly journals Src-family protein tyrosine kinase phosphorylates WNK4 and modulates its inhibitory effect on KCNJ1 (ROMK)

2015 ◽  
Vol 112 (14) ◽  
pp. 4495-4500 ◽  
Author(s):  
Dao-Hong Lin ◽  
Peng Yue ◽  
Orlando Yarborough ◽  
Ute I. Scholl ◽  
Gerhard Giebisch ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Double Mutant ◽  
Protein Tyrosine Kinase ◽  
Tyrosine Phosphatase ◽  
Inhibitory Effect ◽  
Wild Type ◽  
Distal Nephron ◽  
Protein Tyrosine ◽  
Family Protein

With-no-lysine kinase 4 (WNK4) inhibits the activity of the potassium channel KCNJ1 (ROMK) in the distal nephron, thereby contributing to the maintenance of potassium homeostasis. This effect is inhibited via phosphorylation at Ser1196 by serum/glucocorticoid-induced kinase 1 (SGK1), and this inhibition is attenuated by the Src-family protein tyrosine kinase (SFK). Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr1092, Tyr1094, and Tyr1143, and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4. Mutation of Tyr1092 or Tyr1143 to phenylalanine decreased the association of c-Src or PTP-1D with WNK4, respectively. Moreover, the Tyr1092Phe mutation markedly reduced ROMK inhibition by WNK4; this inhibition was completely absent in the double mutant WNK4Y1092/1094F. Similarly, c-Src prevented SGK1-induced phosphorylation of WNK4 at Ser1196, an effect that was abrogated in the double mutant. WNK4Y1143F inhibited ROMK activity as potently as wild-type (WT) WNK4, but unlike WT, the inhibitory effect of WNK4Y1143F could not be reversed by SGK1. The failure to reverse WNK4Y1143F-induced inhibition of ROMK by SGK1 was possibly due to enhancing endogenous SFK effect on WNK4 by decreasing the WNK4–PTP-1D association because inhibition of SFK enabled SGK1 to reverse WNK4Y1143F-induced inhibition of ROMK. We conclude that WNK4 is a substrate of SFKs and that the association of c-Src and PTP-1D with WNK4 at Tyr1092 and Tyr1143 plays an important role in modulating the inhibitory effect of WNK4 on ROMK.

scholarly journals Regulation of the interaction of nicotinic acetylcholine receptors with the cytoskeleton by agrin-activated protein tyrosine kinase.

1995 ◽  
Vol 128 (6) ◽  
pp. 1121-1129 ◽  
Author(s):  
B G Wallace
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Nicotinic Acetylcholine Receptors ◽  
Protein Tyrosine Phosphatase ◽  
Acetylcholine Receptors ◽  
Protein Tyrosine Kinase ◽  
Tyrosine Phosphatase ◽  
Beta Subunit ◽  
Nicotinic Acetylcholine ◽  
Protein Tyrosine

Agrin induces the accumulation of nicotinic acetylcholine receptors (AChRs) in the myofiber membrane at synaptic sites in vertebrate skeletal muscle and causes an increase in tyrosine phosphorylation of the AChR beta subunit. To examine further the mechanism of agrin-induced AChR phosphorylation and the relationship between changes in protein phosphorylation and AChR aggregation, the effect of the protein tyrosine phosphatase inhibitor sodium pervanadate was tested on chick myotubes in culture. Pervanadate caused an increase in the phosphotyrosine content of a variety of proteins, including the AChR. Pervanadate also prevented agrin-induced AChR aggregation and slowed the rate at which AChRs were extracted from intact myotubes by mild detergent treatment. The rate at which phosphorylation of the AChR beta subunit and receptor detergent extractability changed following pervanadate-induced phosphatase inhibition was increased by agrin, indicating that agrin activates a protein tyrosine kinase rather than inhibiting a protein tyrosine phosphatase. The present results, taken together with previous findings on the inhibition of agrin-induced AChR aggregation by protein kinase inhibitors, demonstrate that protein tyrosine phosphorylation regulates the formation and stability of AChR aggregates, apparently by strengthening the interaction between AChRs and the cytoskelton.

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