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Science 20 December 1996:
Vol. 274. no. 5295, pp. 2089 - 2091
DOI: 10.1126/science.274.5295.2089
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Reports

Association of Src Tyrosine Kinase with a Human Potassium Channel Mediated by SH3 Domain

Todd C. Holmes, Debra A. Fadool, Ruibao Ren, Irwin B. Levitan *

The human Kv1.5 potassium channel (hKv1.5) contains proline-rich sequences identical to those that bind to Src homology 3 (SH3) domains. Direct association of the Src tyrosine kinase with cloned hKv1.5 and native hKv1.5 in human myocardium was observed. This interaction was mediated by the proline-rich motif of hKv1.5 and the SH3 domain of Src. Furthermore, hKv1.5 was tyrosine phosphorylated, and the channel current was suppressed, in cells coexpressing v-Src. These results provide direct biochemical evidence for a signaling complex composed of a potassium channel and a protein tyrosine kinase.

T. C. Holmes, D. A. Fadool, I. B. Levitan, Department of Biochemistry and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02254, USA.
R. Ren, Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02254, USA.
*   To whom correspondence should be addressed.


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J. Physiol. 512, 109-118
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A Model for Signal Transduction during Gamete Release in the Fucoid Alga Pelvetia compressa.
G. Anthony Pearson and S. Howard Brawley (1998)
Plant Physiology 118, 305-313
   Abstract »    Full Text »
Modulation of Olfactory Bulb Neuron Potassium Current by Tyrosine Phosphorylation.
D. A. Fadool and I. B. Levitan (1998)
J. Neurosci. 18, 6126-6137
   Abstract »    Full Text »    PDF »
Lasp-1 is a regulated phosphoprotein within the cAMP signaling pathway in the gastric parietal cell.
C. S. Chew, J. A. Parente Jr., C.-J. Zhou, E. Baranco, and X. Chen (1998)
Am J Physiol Cell Physiol 275, C56-C67
   Abstract »    Full Text »    PDF »
Activation of protein tyrosine kinase PYK2 by the m1 muscarinic acetylcholine receptor.
J. S. Felsch, T. G. Cachero, and E. G. Peralta (1998)
PNAS 95, 5051-5056
   Abstract »    Full Text »    PDF »
Evidence for Direct Physical Association between a K+ Channel (Kir6.2) and an ATP-Binding Cassette Protein (SUR1) Which Affects Cellular Distribution and Kinetic Behavior of an ATP-Sensitive K+ Channel.
E. Lorenz, A. E. Alekseev, G. B. Krapivinsky, A. J. Carrasco, D. E. Clapham, and A. Terzic (1998)
Mol. Cell. Biol. 18, 1652-1659
   Abstract »    Full Text »    PDF »
Modulation of Voltage-dependent Ca2+ Channels in Rabbit Colonic Smooth Muscle Cells by c-Src and Focal Adhesion Kinase.
X.-Q. Hu, N. Singh, D. Mukhopadhyay, and H. I. Akbarali (1998)
J. Biol. Chem. 273, 5337-5342
   Abstract »    Full Text »    PDF »
Growth Factor Receptor Tyrosine Kinases Acutely Regulate Neuronal Sodium Channels through the Src Signaling Pathway.
M. D. Hilborn, R. R. Vaillancourt, and S. G. Rane (1998)
J. Neurosci. 18, 590-600
   Abstract »    Full Text »    PDF »
Expression of Voltage-Gated Potassium Channels Decreases Cellular Protein Tyrosine Phosphorylation.
T. C. Holmes, K. Berman, J. E. Swartz, D. Dagan, and I. B. Levitan (1997)
J. Neurosci. 17, 8964-8974
   Abstract »    Full Text »    PDF »
Modulation of Rod Photoreceptor Cyclic Nucleotide-Gated Channels by Tyrosine Phosphorylation.
E. Molokanova, B. Trivedi, A. Savchenko, and R. H. Kramer (1997)
J. Neurosci. 17, 9068-9076
   Abstract »    Full Text »    PDF »
Modulation of the Kv1.3 Potassium Channel by Receptor Tyrosine Kinases.
M. R. Bowlby, D. A. Fadool, T. C. Holmes, and I. B. Levitan (1997)
J. Gen. Physiol. 110, 601-610
   Abstract »    Full Text »    PDF »
Phosphorylation of the Kv2.1 K+ Channel Alters Voltage-Dependent Activation.
H. Murakoshi, G. Shi, R. H. Scannevin, and J. S. Trimmer (1997)
Mol. Pharmacol. 52, 821-828
   Abstract »    Full Text »
Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src-/- mutant mice.
P. L. Schwartzberg, L. Xing, O. Hoffmann, C. A. Lowell, L. Garrett, B. F. Boyce, and H. E. Varmus (1997)
Genes & Dev. 11, 2835-2844
   Abstract »    Full Text »    PDF »
Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung.
G. B. Pier, M. Grout, and T. S. Zaidi (1997)
PNAS 94, 12088-12093
   Abstract »    Full Text »    PDF »
Human Homologue of the Drosophila Discs Large Tumor Suppressor Binds to p56lck Tyrosine Kinase and Shaker Type Kv1.3 Potassium Channel in T Lymphocytes.
T. Hanada, L. Lin, K. G. Chandy, S. S. Oh, and A. H. Chishti (1997)
J. Biol. Chem. 272, 26899-26904
   Abstract »    Full Text »    PDF »
Lysophosphatidylcholine Modulates Cardiac INa via Multiple Protein Kinase Pathways.
C. L. Watson and M. R. Gold (1997)
Circ. Res. 81, 387-395
   Abstract »    Full Text »
Tyrosine Phosphorylation of Connexin 43 by v-Src Is Mediated by SH2 and SH3 Domain Interactions.
M. Y. Kanemitsu, L. W. M. Loo, S. Simon, A. F. Lau, and W. Eckhart (1997)
J. Biol. Chem. 272, 22824-22831
   Abstract »    Full Text »    PDF »
Requirement for Tyrosine Phosphatase during Serotonergic Neuromodulation by Protein Kinase C.
S. Catarsi and P. Drapeau (1997)
J. Neurosci. 17, 5792-5797
   Abstract »    Full Text »    PDF »
Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding.
M. Colledge and S. C. Froehner (1997)
J. Neurosci. 17, 5038-5045
   Abstract »    Full Text »    PDF »
Simultaneous Binding of Two Protein Kinases to a Calcium-Dependent Potassium Channel.
J. Wang, Y. Zhou, H. Wen, and I. B. Levitan (1999)
J. Neurosci. 19, RC4
   Abstract »    Full Text »    PDF »
Enhanced Activity of a Large Conductance, Calcium-sensitive K+ Channel in the Presence of Src Tyrosine Kinase.
S. Ling, G. Woronuk, L. Sy, S. Lev, and A. P. Braun (2000)
J. Biol. Chem. 275, 30683-30689
   Abstract »    Full Text »    PDF »
A Catalytically Inactive Mutant of Type I cGMP-dependent Protein Kinase Prevents Enhancement of Large Conductance, Calcium-sensitive K+ Channels by Sodium Nitroprusside and cGMP.
R. D. Swayze and A. P. Braun (2001)
J. Biol. Chem. 276, 19729-19737
   Abstract »    Full Text »    PDF »
Isoform-specific Localization of Voltage-gated K+ Channels to Distinct Lipid Raft Populations. TARGETING OF Kv1.5 TO CAVEOLAE.
J. R. Martens, N. Sakamoto, S. A. Sullivan, T. D. Grobaski, and M. M. Tamkun (2001)
J. Biol. Chem. 276, 8409-8414
   Abstract »    Full Text »    PDF »
Regulation of the L-type Calcium Channel by alpha 5beta 1 Integrin Requires Signaling between Focal Adhesion Proteins.
X. Wu, G. E. Davis, G. A. Meininger, E. Wilson, and M. J. Davis (2001)
J. Biol. Chem. 276, 30285-30292
   Abstract »    Full Text »    PDF »
A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors.
M. N. Nitabach, D. A. Llamas, R. C. Araneda, J. L. Intile, I. J. Thompson, Y. I. Zhou, and T. C. Holmes (2001)
PNAS 98, 705-710
   Abstract »    Full Text »    PDF »
Direct inhibition of the cloned Kv1.5 channel by AG-1478, a tyrosine kinase inhibitor.
B. H. Choi, J.-S. Choi, D.-J. Rhie, S. H. Yoon, D. S. Min, Y.-H. Jo, M.-S. Kim, and S. J. Hahn (2002)
Am J Physiol Cell Physiol 282, C1461-C1468
   Abstract »    Full Text »    PDF »


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