Protein kinase pathways

Functionally, the Dl-like receptors (Dl, D5) are coupled to the G protein Gas and thus can stimulate adenylyl cyclase. The D2-like receptors (D2, D3, and D4) couple to pertussis toxin sensitive G proteins (Gai/0), and consequently inhibit adenylyl cyclase activity. While the Dl-like receptors almost exclusively signal through Gas-mediated activation of adenylyl cyclase, the D2-like receptors have been reported to modulate the activity of a plethora of signaling molecules and pathways. Many of these actions are mediated through the G(3y subunit. Some of these molecules and pathways include the calcium channels, potassium channels, sodium-hydrogen exchanger, arachidonic acid release, and mitogen-activated protein kinase pathways. 

PKA and PKC are, however, not the only kinases to regulate TRPVl. The Ca /calmodulin-dependent kinase II (CaMKII) sensitizes TRPVl by phosphorylation [57, 58], as does phophatidylinositol 3-kinase (PI3K) via its downstream target AKT [59]. This latter finding links TRPVl to the ERK (extracellular signal-regulated protein kinase) pathway. The non-receptor tyrosine kinase Src likewise potentiates capsaicin-induced currents [60]. 

Ogilvie P, Thelen S, Moepps B, et al. Unusual chemokine receptor antagonism involving a mitogen-activated protein kinase pathway. J Immunol 2004 172 6715-6722. 

The Ras pathway is shown here. Ras is a G-protein that couples signaling from growth factors. The activated receptor is a GNRP that increases the exchange of GDP for GTP and activates the G-protein. Ras GAP inactivates the G-protein. The downstream signal for activated Ras is eventually the mitogen-activated protein kinase pathway (MAPK). 

Johnson, G. L. and Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298 1911-1912,2002. 

Simeonova, P. P. et al., c-Src-dependent activation of the epidermal growth factor receptor and mitogen-activated protein kinase pathway by arsenic. Role in carcinogenesis, J. Biol. Chem., 277, 2945, 2002. 

In the proper cellular context in B cells, NK cells and mast cells, Syk kinase has been shown to transduce cell growth and survival signals by activating PI3K/Akt and Ras/mitogen-activated protein kinase pathways [3,46]. When deregulated, Syk activity can promote myelodysplasias, leukemogenesis, and perhaps viral-media ted cellular transformations [47,48]. By contrast, Syk has also been proposed to function as a tumor suppressor [49]. This is however, based on... 

Xue, J.-F., Liu, Z.-J., Hu, J.-F., Chen, H., Zhang, J.-T., and Chen, N.-H. (2006). Ginsenoside Rbl promotes neurotransmitter release by modulating phosphyrolation of synapsis through a cAMP-dependent protein kinase pathway. Brain Res. 1106, 91-98. 

Cunnick, J.M., Dorsey, J.F., Standley, T., Turkson, J., Kraker, A.J., Fry, D.W., Jove, R., and Wu, J., 1998, Role of tyrosine kinase activity of epidermal growth factor receptor in the lysophosphatidic acid-stimulated mitogen-activated protein kinase pathway, J. Biol. Chem. 273 14468-14475. 

Rakhit, S., Conway, A-M., Tate, R., Bower, T, Pyne, N.J. and Pyne, S., 1999, Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle role of endothelial differentiation gene-1, c-Src tyrosine kinase and phosphoinositide 3-kinase. Biochem. J. 338 643-649. 

Costigan, C., Kolodrubetz, D., and Snyder, M. (1994) NHP6A and NHP6B, which encode HMGl-like proteins, are candidates for downstream components of the yeast SLT2 mitogen-activated protein kinase pathway. Mol. Cell. Biol. 14, 2391-2403. 

Fig. 6. Role of signal transduction pathways in phosphorylating H3 at Ser-10 and Ser-28. The Ras-MAPK (mitogen activated protein kinase) pathway is activated by EGF (epidermal growth factor) and TPA (12-0-tetradecanoylphorbol-13-acetate). UV-B activates both the Ras-MAPK pathway and the p38 kinase pathway (for more information about the signal transduction pathways see http // kinase, oci.utoronto.ca/signallingmap.html).

Robinson, MJ. and Cobb, M.H. Mitogen-activated protein kinase pathways (1997) Curr. Op. Cell. Biol. 9, 180-186... 

Witta SE, Gemmill RM, Hirsch FR et al. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 2006 66 944-950. Walker F, Kato A, Gonez LJ et al. Activation of the Ras/mitogen-activated protein kinase pathway by kinase-defective epidermal growth factor receptors results in cell survival but not proliferation. Mol Cell Biol 1998 18 7192-7204. 

Carrillo, J.J. Ibares, B. Esteban-Gamboa, A. Feliu, J.E. Involvement of both phosphatidylinositol 3-kinase and p44/p42 mitogen-activated protein kinase pathways in the short-term regulation of pyruvate kinase L by insulin. Endocrinology, 142, 1057-1064 (2001)... 

Knall, C. Young, S. Nick, J.A. Buhl, A.M. Worthen, G.S. Johnson, G.L. Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway in human neutrophils. J. Biol. Chem., 271, 2832-2838 (1996)... 

CBi and CB2 seem to couple to inhibitory Gj and/or G0 proteins. CBi receptors are known to effect adenylate cyclase, a variety of potassium and calcium currents, and the mitogen-activated protein kinase pathway. CBi receptors have been shown to activate at least six subtypes of Gj and G0 proteins, supporting reports that they effect a wide variety of intracellular signaling systems. In contrast to CB receptors, CB2 receptors do not seem to effect ion currents directly (Breivogel et al., 2001). 

Khan TA, Bianchi C, Ruel M, Voisine P, Sellke FW (2004) Mitogen-activated protein kinase pathways and cardiac surgery. J Thorac Cardiovasc Surg 127(3) 806-811 Khimenko PL, Moore TM, Hill LW, Wilson PS, Coleman S, Rizzo A, Taylor AE (1995) Adenosine A2 receptors reverse ischemia-reperfusion lung injury independent of P-receptors. J Appl Physiol 78(3) 990-996... 

Yu R, Hebbar Y, Kim DW, Mandlekar S, Pezzuto JM, Kong AN. 2001. Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with mitogen-activated protein kinase pathways. Mol Pharmacol 60 217-224. 

Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. 2005. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer 104 879-890. 

Other putative effects of estrogens include preservation of autoregulatory function, an antioxidant effect, reduction of A(i production and neurotoxicity, reduced excitotoxicity, increased expression of antiapoptotic factor bcl-2, and activation of mitogen-activated protein kinase pathways. Also, there is overwhelming data indicating that estrogens enhance survival of neurons both in vitro and in vivo (Green and Simpkins, 2000). 

Lopez-Pedrera, C., Buendia, P., Cuadrado, MJ., Siendones, E., Aguirre, M.A., Barbarroja, N., Montiel-Duarte, C., Torres, A., Khamashta, M., and F. Velasco, 2006, Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF-kappaB/Rel proteins via the p38 mitogen-activated protein kinase pathway, and of the MEK-l/ERK pathway.Arthritis Rheum. 54(1) 301—11. 

Yasuda, S., Bohgaki, M., Atsumi, T., and T. Koike, 2005, Pathogenesis of antiphospholipid antibodies impairment of fibrinolysis and monocyte activation via die p38 mitogen-activated protein kinase pathway.Immunobiology. 210(10) 775-80. 

Wu, G. Y., Deisseroth, K. and Tsien, R. W., 2001, Activity-dependent CREB phosphorylation convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway, Proc Natl Acad Sci USA, 98, pp 2808—13. 

Suzuki T, Mitake S, Murata S. Presence of up-stream and downstream components of a mitogen-activated protein kinase pathway in the PSD of the rat forebrain. Brain Res 1999 840 36 14. 

Hsu, S. et al. Green tea polyphenols reduced the psoriasiform lesions and regulate caspase 14 by the mitogen-activated protein kinase pathways. Experimental Dermatology. 16(8), 678, 2007. 

Geraldes R Sirois MG, TanguayJE Specific contribution of estrogen receptors on mitogen-activated protein kinase pathways and vascular cell activation. Circ Res 2003 93 399-405. 

The mitogen-activated protein kinase pathway (MAPK) on the right side of Figure 11.1 is also activated via the adaptor protein GRB-2 after insulin binds to its receptor. This activated kinase pathway eventually leads to the phosphorylation of... 

Watts SW. Activation of the mitogen-activated protein kinase pathway via the 5-HT2A receptor. Ann NY Acad Sci 1998 861 162-168. 

Faure M, Voyno-Yasenetskaya TA, Bourne HR. 1994. cAMP and beta gamma subunits of het-erotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J Biol Chem 269 7851-7854. 

HordijkPL, VerlaanI, JalinkK, vanCorvenEJ, Moolenaar WH.1994. cAMP abrogates the p21ras-mitogen-activated protein kinase pathway in fibroblasts. J Biol Chem 269 35334—35338. 

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