3pK, a Novel Mitogen-Activated Protein (MAP) Kinase-Activated Protein Kinase, Is Targeted by Three MAP Kinase Pathways

The extracellular-signal-regulated protein kinases (Erks) are required for UV-induced AP-1 activation in JB6 cells

“…The Ras?Raf?MEK?Erks cascade is the signaling cascade that leads to Erks activation. Previous studies have found that cell exposure to UV irradiation caused activation of both Erks (Denhardt, 1996;PageÁ s et al, 1993) and JNKs (Adler et al, 1995(Adler et al, , 1996De rijard et al, 1994;Van Blesen et al, 1995;Verheij et al, 1996;Wan et al, 1996) pathways, but the extent of activation between these two pathways was di erent (Canman and Kasten, 1996;Denhardt, 1996;Ludwig et al, 1996;Radler-Pohl et al, 1993). JNKs were e ciently activated in cells exposed to UV, while UV irradiation only induced weak activation of Erks.…”

“…It is believed that Erks are strongly activated and play a critical role in transmitting signals initiated by 12-0-tetradecanoylphorbol-13-acetate (TPA) and growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) (Cowley et al, 1994;Dalton and Treisman, 1992;L'Allemain et al, 1992;PageÁ s et al, 1993;Robbins et al, 1993;Wan et al, 1996;Xia et al, 1995). Whereas the JNKs/SAPKs and P38 kinases are potently activated by various forms of stress, such as ultraviolet light (UV), heat shock and in¯ammation (Adler et al, 1995(Adler et al, , 1996BuÈ scher et al, 1988; Denhardt, 1996;Ludwig et al, 1996;Minden et al, 1994; Sa nchez et al, 1994), the activation of these pathways is not mutually exclusive. For example, heat shock and UV irradiation partially activate the Erk1/Erk2 cascade and EGF partially activates the JNKs/SAPKs pathway (Denhardt, 1996, Minden et al, 1994.…”

Signaling by dual specificity kinases

“…Diverse stimuli including in¯ammatory cytokines, osmotic stress, UVirradiation and heat-shock have been shown to activate MKK3 . Activation of MEKK3-p38MAPK signaling pathway leads to the activation of di erent kinases such as MAPKAP-2 (Stokoe et al, 1992;Rouse et al, 1994;Freshney et al, 1994), MAPKAP-3 (Ludwig et al, 1996), and MNK1/2 kinases (Waskiewicz et al, 1997;Fukunaga and Hunter, 1997). Similar to ERKs the phosphorylated p38MAPK translocates to the nucleus and phosphorylates the transcription factors such as ATF2 , CREB (Tan et al, 1996), CHOP (Wang and Ron, 1996), and MEF2C (Han et al, 1997a).…”

Stimulation of urokinase-type plasminogen activator receptor expression by PMA requires JNK1-dependent and -independent signaling modules

“…Further, Protein Kinase C, the receptor for PMA, binds to and activates c-Raf-1 leading to ERK activation (Cai et al, 1997;Marquardt et al, 1994;Sozeri et al, 1992;Berra et al, 1995;Sauma and Friedman, 1996). On the other hand, several studies have demonstrated that JNK activity in the parallel signaling cascade is either not stimulated or only weakly activated by this phorbol ester Minden et al, 1994b;Hibi et al, 1993;Ludwig et al, 1996;Bogoyevitch et al, 1995;Cano et al, 1995). While the cited studies would predict that the e ect of PMA on u-PAR expression is mediated through the c-Raf-1-ERK pathway, it is now becoming apparent that these signaling modules are by no means linear and, in fact, there is increasing evidence for cross-talk between the various cascades (Bogoyevitch et al, 1995).…”