Links between Pyk2 and Map Kinases
This diagram is a compilation of Pyk2 effort cascades. In specific cell types the receptor and effoectors will vary. Binding of a transmembrane receptor triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to Pyk2 and further to the small G protein Rac1. In turn, Rac1 initiatates the JNK cascade, starting with PAK follwed by MEKK1, SEK1, and JNK. JNK activation causes induction of c-Jun gene binding. Pyk2 stimulation has also been shown to activate MKK3 leading to activation of p38. The other major mitogen activated kinase cascade for ERK1/2 is stimulated via RAS, RAF and MEKK1/2.
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REFERENCES: Blaukat A, Ivankovic-Dikic I, Gronroos E, Dolfi F, Tokiwa G, Vuori K, Dikic I. Adaptor proteins Grb2 and Crk Couple Pyk2 with Activation of Specific Mitogen-activated Protein Kinase Cascades. Biochem. J., vol 274(21), May 1999, 14893-901. Enslen H, Tokumitsu H, Stork P, Davis R, Soderling T. Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade. PNAS, vol 93, October 1996, 10803-08. Kholodenko, Boris. MAP kinase cascade signaling and endocytic trafficking: a marriage of convenience? TRENDS in Cell Biology, vol 12(4), April 2002, 173-77. Pandey P, Avraham S, Kumar S, Nakazawa A, Place A, Ghanem L, Rana A, Kumar V, Majumder PK, Avraham H, Davis RJ, Kharbanda S. Activation of p38 mitogen-activated protein kinase by PYK2/related adhesion focal tyrosine kinase-dependent mechanism. Biochem. J., vol 274(15), April 1999, 10140-44. Weber SM, Chen JM, Levitz SM. Inhibition of mitogen-activated protein kinase signaling by chloroquine. J Immunology, vol 168(10), May 2002, 5303-09.
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