Construction, Analysis and Visualization of a Large-scale Signaling Network in Hippocampal Neuronal Mammalian Cells

Source: Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong NJ, Weng G, Ram PT, Rice JJ, Kershenbaum A, Stolovitzky GA, Blitzer RD, Iyengar R. Formation of regulatory patterns during signal propagation in a Mammalian cellular network. Science. 2005 Aug 12;309(5737):1078-83.
PMID: 16099987 | PMCID: PMC3032439 | EndNote Citation

Index of Nodes

PKA


Average path length to all other components: 2.92751
Clustering coefficient: 0.012549
Grid coefficient: 0.00104915

Swiss-Prot Human Accession Code: P17612
Swiss-Prot Mouse Accession Code: P05132

List of interactions:

Source:PKAType of molecule:Kinase Location:Cytosol
Target:P53Type of molecule:TF Location:Nucleus
Type of interaction:Phosphorylation Effect:+
References:
1. V. Adler, M. R. Pincus, T. Minamoto, et al., Proc. Natl. Acad. Sci. U. S. A. 94, 1686 (1997). PubMed ID: 9050839

Source:PKAType of molecule:Kinase Location:Cytosol
Target:RCSType of molecule:Inhibitor Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. S. V. Rakhilin, P. A. Olson, A. Nishi, et al., Science. 306, 698 (2004). PubMed ID: 15499021

Source:PKAType of molecule:Kinase Location:Cytosol
Target:BADType of molecule:Bcl2Family Location:Mitochondria
Type of interaction:Phosphorylation Effect:_
References:
1. D. R. Kaplan, F. D. Miller, Curr. Opin. Neurobiol. 10, 381 (2000). PubMed ID: 10851172
2. J. M. Lizcano, N. Morrice, P. Cohen, Biochem. J. 349, 547 (2001). PubMed ID: 10880354
3. H. Harada, B. Becknell, M. Wilm, et al., Mol. Cell. 3, 413 (1999). PubMed ID: 10230394

Source:PKAType of molecule:Kinase Location:Cytosol
Target:ATF1Type of molecule:TF Location:Nucleus
Type of interaction:Phosphorylation Effect:+
References:
1. R. P. Rehfuss, K. M. Walton, M. M. Loriaux, et al., J. Biol. Chem. 266, 18431 (1991). PubMed ID: 1655749

Source:PKAType of molecule:Kinase Location:Cytosol
Target:CREBType of molecule:TF Location:Nucleus
Type of interaction:Phosphorylation Effect:+
References:
1. M. R. Montminy, K. A. Sevarino, J. A. Wagner, et al., Proc. Natl. Acad. Sci. U. S. A. 83, 6682 (1986). PubMed ID: 2875459
2. M. R. Montminy, L. M. Bilezikjian, Nature. 328, 175 (1987). PubMed ID: 2885756

Source:cAMPType of molecule:Messenger Location:Cytosol
Target:PKAType of molecule:Kinase Location:Cytosol
Type of interaction:Binding Effect:+
References:
1. D. V. Madison, R. C. Malenka, R. A. Nicoll, Nature. 321, 695 (1986). PubMed ID: 2423884

Source:PKAType of molecule:Kinase Location:Cytosol
Target:SYNAPSINType of molecule:Vesicle Location:Vesicles
Type of interaction:Phosphorylation Effect:_
References:
1. A. J. Czernik, D. T. Pang, P. Greengard, Proc. Natl. Acad. Sci. U. S. A. 84, 7518 (1987). PubMed ID: 3118371
2. Y. Tu, S. K. Nayak, J. Woodson, et al., J. Biol. Chem. 278, 52273 (2003). PubMed ID: 14557263
3. R. Goold, K. M. Chan, A. J. Baines, Biochemistry. 34, 1912 (1995). PubMed ID: 7849051

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PLCGAMMAType of molecule:Phospholipase Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. U. H. Kim, J. W. Kim, S. G. Rhee, J. Biol. Chem. 264, 20167 (1990). PubMed ID: 2479646

Source:PKAType of molecule:Kinase Location:Cytosol
Target:NFKBType of molecule:TF Location:Nucleus
Type of interaction:Phosphorylation Effect:+
References:
1. S. H. Yu, W. C. Chiang, H. M. Shih, et al., J. Mol. Med. 82, 621 (2004). PubMed ID: 15197457

Source:PKAType of molecule:Kinase Location:Cytosol
Target:IP3RType of molecule:Channel Location:ER
Type of interaction:Phosphorylation Effect:_
References:
1. S. Supattapone, S. K. Danoff, A. Theibert, et al., Proc. Natl. Acad. Sci. U. S. A. 85, 8747 (1988). PubMed ID: 2847175
2. C. D. Ferris, A. M. Cameron, D. S. Bredt, et al., Biochem. Biophys. Res. Commun. 175, 192 (1991). PubMed ID: 1847804

Source:PKAType of molecule:Kinase Location:Cytosol
Target:NOSType of molecule:Synthase Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. J. L. Dinerman, J. P. Steiner, T. M. Dawson, et al., Neuropharmacology. 33, 1245 (1995). PubMed ID: 7532810

Source:PKAType of molecule:Kinase Location:Cytosol
Target:RABPHILINType of molecule:Vesicle Location:Vesicles
Type of interaction:Phosphorylation Effect:+
References:
1. E. M. Fykse, C. Li, T. C. Sudhof, J. Neurosci. 15, 2385 (1995). PubMed ID: 7891174
2. G. Lonart, T. C. Sudhof, J. Neurosci. 18, 634 (1998). PubMed ID: 9425005

Source:PKAType of molecule:Kinase Location:Cytosol
Target:AKAPType of molecule:Adapter Location:Cytosol
Type of interaction:Binding Effect:0
References:
1. T. M. Klauck, M. C. Faux, K. Labudda, et al., Science. 271, 1589 (1996). PubMed ID: 8599116
2. D. W. Carr, R. E. Stofko-Hahn, I. D. Fraser, et al., J. Biol. Chem. 267, 16816 (1992). PubMed ID: 1512224

Source:PKAType of molecule:Kinase Location:Cytosol
Target:RAF1Type of molecule:Kinase Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. M. F. Sidovar, P. Kozlowski, J. W. Lee, et al., J. Biol. Chem. 275, 28688 (2000). PubMed ID: 10862777
2. S. Hafner, H. S. Adler, H. Mischak, et al., Mol. Cell. Biol. 14, 6696 (1994). PubMed ID: 7935389
3. W. M. Yee, P. F. Worley, Mol. Cell. Biol. 17, 921 (1997). PubMed ID: 9001246

Source:PKAType of molecule:Kinase Location:Cytosol
Target:RAP1Type of molecule:GTPase Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. C. D. Hu, K. Kariya, T. Okada, et al., J. Biol. Chem. 274, 48 (1999). PubMed ID: 9867809
2. D. Altschuler, E. G. Lapetina, J. Biol. Chem. 268, 7527 (1993). PubMed ID: 8463283

Source:PKAType of molecule:Kinase Location:Cytosol
Target:CAMKKType of molecule:Kinase Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. M. Matsushita, A. C. Nairn, J. Biol. Chem. 274, 10086 (1999). PubMed ID: 10187789

Source:PKAType of molecule:Kinase Location:Cytosol
Target:SPINOPHILINType of molecule:Cytoskeleton Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. L. C. Hsieh-Wilson, F. Benfenati, G. L. Snyder, et al., J. Biol. Chem. 278, 1186 (2003). PubMed ID: 12417592

Source:PKAType of molecule:Kinase Location:Cytosol
Target:bRAFType of molecule:Kinase Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. W. Qiu, S. Zhuang, et al., J. Biol. Chem. 275, 31921 (2000). PubMed ID: 10931830

Source:PKAType of molecule:Kinase Location:Cytosol
Target:GLYRType of molecule:Receptor Location:Membrane
Type of interaction:Phosphorylation Effect:+
References:
1. M. L. Vaello, A. Ruiz-Gomez, J. Lerma, et al., J. Biol. Chem. 269, 2002 (1994). PubMed ID: 8294452

Source:PKAType of molecule:Kinase Location:Cytosol
Target:CBPType of molecule:TF Location:Nucleus
Type of interaction:Phosphorylation Effect:+
References:
1. A. Constantinescu, M. Wu, O. Asher, et al., J. Biol. Chem. 279, 43321 (2004). PubMed ID: 15299023

Source:PKAType of molecule:Kinase Location:Cytosol
Target:DARPP32Type of molecule:Inhibitor Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. T. Kurihara, R. M. Lewis, J. Eisler, et al., J. Neurosci. 8, 508 (1988). PubMed ID: 3339428
2. S. I. Walaas, D. W. Aswad, P. Greengard, Nature. 301, 69 (1983). PubMed ID: 6296685
3. H. C. Hemmings, et al., J. Neurosci. 4, 99 (1984). PubMed ID: 6319628

Source:PKAType of molecule:Kinase Location:Cytosol
Target:BETA2ARType of molecule:Receptor Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. J. L. Benovic, L. J. Pike, R. A. Cerione, et al., J. Biol. Chem. 260, 7094 (1985). PubMed ID: 2987243

Source:PKAType of molecule:Kinase Location:Cytosol
Target:D1RType of molecule:Receptor Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. D. Zamanillo, E. Casanova, A. Alonso-Llamazares, et al., Neurosci. Lett. 188, 183 (1995). PubMed ID: 7609904

Source:PKAType of molecule:Kinase Location:Cytosol
Target:KV42Type of molecule:Channel Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. L. A. Schrader, A. E. Anderson, A. Mayne, et al., J. Neurosci. 22, 10123 (2002). PubMed ID: 12451113

Source:PKAType of molecule:Kinase Location:Cytosol
Target:TAUType of molecule:Activator Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. M. Pierre, J. Nunez, Biochem. Biophys. Res. Commun. 115, 212 (1983). PubMed ID: 6412713
2. J. M. Litersky, G. V. Johnson, J. Biol. Chem. 267, 1563 (1992). PubMed ID: 1730702

Source:PKAType of molecule:Kinase Location:Cytosol
Target:KARType of molecule:Channel Location:Membrane
Type of interaction:Phosphorylation Effect:+
References:
1. L. A. Raymond, C. D. Blackstone, R. L. Huganir, Nature. 361, 637 (1993). PubMed ID: 8094892

Source:PKAType of molecule:Kinase Location:Cytosol
Target:AMPARType of molecule:Channel Location:Membrane
Type of interaction:Phosphorylation Effect:+
References:
1. A. M. Vanhoose, D. G. Winder, J. Neurosci. 23, 5827 (2003). PubMed ID: 12843287

Source:PKAType of molecule:Kinase Location:Cytosol
Target:MAP2Type of molecule:Cytoskeleton Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. S. I. Walaas, A. C. Nairn, J. Mol. Neurosci. 1, 117 (1990). PubMed ID: 2561875
2. A. Alexa, G. Schmidt, P. Tompa, et al., Biochemistry. 41, 12427 (2002). PubMed ID: 12369833
3. G. V. Johnson, V. G. Foley, J. Neurosci. Res. 34, 642 (1993). PubMed ID: 8391085

Source:PKAType of molecule:Kinase Location:Cytosol
Target:ADDUCINType of molecule:Adapter Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. Y. Matsuoka, C. A. Hughes, V. Bennett, J. Biol. Chem. 271, 25157 (1996). PubMed ID: 8810272

Source:PKAType of molecule:Kinase Location:Cytosol
Target:FILAMINType of molecule:Cytoskeleton Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. D. Jay, E. J. Garcia, l. a. de, et al., Mol. Cell. Biochem. 260, 49 (2004). PubMed ID: 15228085
2. D. Wallach, P. J. Davies, I. Pastan, J. Biol. Chem. 253, 4739 (1978). PubMed ID: 207708

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PDE3AType of molecule:PDE Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. C. H. Macphee, D. H. Reifsnyder, T. A. Moore, et al., J. Biol. Chem. 263, 10353 (1988). PubMed ID: 2839485

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PDE3BType of molecule:PDE Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. C. H. Macphee, D. H. Reifsnyder, T. A. Moore, et al., J. Biol. Chem. 263, 10353 (1988). PubMed ID: 2839485

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PDE4DType of molecule:PDE Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. S. P. Alexander, A. Mathie, J. A. Peters, Br. J. Pharmacol. 141, S1 (2004). PubMed ID: 15082510

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PDE5AType of molecule:PDE Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. S. P. Alexander, A. Mathie, J. A. Peters, Br. J. Pharmacol. 141, S1 (2004). PubMed ID: 15082510

Source:PKAType of molecule:Kinase Location:Cytosol
Target:NMDARType of molecule:Receptor Location:Membrane
Type of interaction:Phosphorylation Effect:+
References:
1. A. S. Leonard, J. W. Hell, J. Biol. Chem. 272, 12107 (1997). PubMed ID: 9115280

Source:PKAType of molecule:Kinase Location:Cytosol
Target:SNAPINType of molecule:Vesicle Location:Vesicles
Type of interaction:Phosphorylation Effect:+
References:
1. P. Thakur, D. R. Stevens, Z. H. Sheng, et al., J. Neurosci. 24, 6476 (2004). PubMed ID: 15269257

Source:PKIType of molecule:Inhibitor Location:Cytosol
Target:PKAType of molecule:Kinase Location:Cytosol
Type of interaction:Binding Effect:_
References:
1. S. R. Olsen, M. D. Uhler, Mol. Endocrinol. 5, 1246 (1992). PubMed ID: 1770951

Source:PKAType of molecule:Kinase Location:Cytosol
Target:I1Type of molecule:Inhibitor Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. S. Endo, X. Zhou, J. Connor, et al., Biochemistry. 35, 5220 (1996). PubMed ID: 8611507

Source:PKAType of molecule:Kinase Location:Cytosol
Target:YOTIAOType of molecule:Adapter Location:Cytosol
Type of interaction:Binding Effect:0
References:
1. R. S. Westphal, S. J. Tavalin, J. W. Lin, et al., Science. 285, 93 (1999). PubMed ID: 10390370

Source:AKAP15Type of molecule:Adapter Location:Cytosol
Target:PKAType of molecule:Kinase Location:Cytosol
Type of interaction:Binding Effect:0
References:
1. P. C. Gray, B. D. Johnson, R. E. Westenbroek, et al., Neuron. 20, 1017 (1998). PubMed ID: 9620705

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PMCAType of molecule:Pump Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. L. Zylinska, D. Guerini, E. Gromadzinska, et al., Biochim. Biophys. Acta. 1448, 99 (1999). PubMed ID: 9824678

Source:PKAType of molecule:Kinase Location:Cytosol
Target:STEPType of molecule:Phosphatase Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. S. Paul, G. L. Snyder, H. Yokakura, et al., J. Neurosci. 20, 5630 (2000). PubMed ID: 10908600

Source:PKAType of molecule:Kinase Location:Cytosol
Target:LTYPECAType of molecule:Channel Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. M. A. Davare, M. C. Horne, J. W. Hell, J. Biol. Chem. 275, 39710 (2001). PubMed ID: 10984483
2. Y. Lai, M. J. Seagar, M. Takahashi, et al., J. Biol. Chem. 265, 20839 (1991). PubMed ID: 2174428
3. M. A. Davare, F. Dong, C. S. Rubin, et al., J. Biol. Chem. 274, 30280 (1999). PubMed ID: 10514522
4. J. W. Hell, C. T. Yokoyama, L. J. Breeze, et al., EMBO. J. 14, 3036 (1995). PubMed ID: 7621818

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PLCBETAType of molecule:Phospholipase Location:Cytosol
Type of interaction:Phosphorylation Effect:_
References:
1. M. Liu, M. I. Simon, Nature. 382, 83 (1996). PubMed ID: 8657310
2. C. Yue, K. L. Dodge, G. Weber, et al., J. Biol. Chem. 273, 18023 (1998). PubMed ID: 9660757

Source:PKAType of molecule:Kinase Location:Cytosol
Target:NFATType of molecule:TF Location:Nucleus
Type of interaction:Phosphorylation Effect:_
References:
1. C. W. Chow, R. J. Davis, Mol. Cell. Biol. 20, 702 (2000). PubMed ID: 10611249

Source:PKAType of molecule:Kinase Location:Cytosol
Target:MGLUR7Type of molecule:Receptor Location:Membrane
Type of interaction:Phosphorylation Effect:+
References:
1. S. D. Sorensen, T. A. Macek, Z. Cai, et al., Mol. Pharmacol. 61, 1303 (2002). PubMed ID: 12021391

Source:PKAType of molecule:Kinase Location:Cytosol
Target:KIR23Type of molecule:Channel Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. N. A. Cohen, J. E. Brenman, S. H. Snyder, et al., Neuron. 17, 759 (1996). PubMed ID: 8893032

Source:PKAType of molecule:Kinase Location:Cytosol
Target:PQCaChType of molecule:Channel Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. L. Wu, C. S. Bauer, X. G. Zhen, et al., Nature. 419, 947 (2002). PubMed ID: 12410316

Source:PKAType of molecule:Kinase Location:Cytosol
Target:MST3Type of molecule:Adapter Location:Cytosol
Type of interaction:Phosphorylation Effect:+
References:
1. T. H. Zhou, K. Ling, J. Guo, et al., J. Biol. Chem. 275, 2513 (2000). PubMed ID: 10644707

Source:PKAType of molecule:Kinase Location:Cytosol
Target:GABAARType of molecule:Receptor Location:Membrane
Type of interaction:Phosphorylation Effect:_
References:
1. N. M. Porter, R. E. Twyman, M. D. Uhler, et al., Neuron. 5, 789 (1991). PubMed ID: 2176510
2. S. J. Moss, C. A. Doherty, R. L. Huganir, J. Biol. Chem. 267, 14470 (1992). PubMed ID: 1321150
3. S. J. Moss, T. G. Smart, C. D. Blackstone, et al., Science. 257, 661 (1992). PubMed ID: 1323140

Source:PKAType of molecule:Kinase Location:Cytosol
Target:RIMType of molecule:Adapter Location:Vesicles
Type of interaction:Phosphorylation Effect:+
References:
1. G. Lonart, S. Schoch, P. S. Kaeser, et al., Cell. 115, 49 (2003). PubMed ID: 14532002