The two Drosophila p38 genes exhibit different embryonic expression patterns. Mpk2 (p38a) mRNA expression occurs predominantly at the preblastoderm stage, indicating a high level of maternal deposition. Zygotic expression is below the detectable level during most of embryonic development. However, Northern analysis demonstrates the presence of low mRNA levels throughout development. At stage 16, there is a low level of staining in the posterior region, which may correspond to the developing hindgut. The preblastoderm staining indicates that Mpk2 may participate in early embryonic development. The p38b gene is expressed throughout embryonic development. There is a high level of maternal deposition, and at later stages, zygotic expression is present in most of the tissues. At midembryogenesis, higher levels of mRNA are detected in the developing anterior and posterior midguts. The expression pattern of p38b is very similar to that of the two MKKs, which also have high maternal deposition in early embryos and zygotic expression in the midguts. One noteworthy difference between the two MKKs is that MKK4 expression is sustained in the ventral nerve cord, while MKK3 (Licorne) expression is less detectable in this tissue but is more prominent in the midgut. Since each of these kinases is deposited maternally, they may all be involved in early development. At later stages, p38b may be the primary mediator of the p38 MAPK pathway, particularly in the developing midgut (Z. Han, 1998).

The MAP kinase p38 is part of Drosophila melanogaster's circadian clock

All organisms have to adapt to acute as well as to regularly occurring changes in the environment. To deal with these major challenges organisms evolved two fundamental mechanisms: the p38 mitogen-activated protein kinase (MAPK) pathway, a major stress pathway for signaling stressful events, and circadian clocks to prepare for the daily environmental changes. Both systems respond sensitively to light. Recent studies in vertebrates and fungi indicate that p38 is involved in light-signaling to the circadian clock providing an interesting link between stress-induced and regularly rhythmic adaptations of animals to the environment, but the molecular and cellular mechanisms remained largely unknown. This study demonstrates by immunocytochemical means that p38 is expressed in Drosophila melanogaster's clock neurons and that it is activated in a clock-dependent manner. Surprisingly, it was found that p38 is most active under darkness and, besides its circadian activation, additionally gets inactivated by light. Moreover, locomotor activity recordings revealed that p38 is essential for a wild-type timing of evening activity and for maintaining approximately 24 h behavioral rhythms under constant darkness: flies with reduced p38 activity in clock neurons, delayed evening activity and lengthened the period of their free-running rhythms. Furthermore, nuclear translocation of the clock protein Period was significantly delayed on the expression of a dominant-negative form of p38b in Drosophila's most important clock neurons. Western Blots revealed that p38 affects the phosphorylation degree of Period, what is likely the reason for its effects on nuclear entry of Period. In vitro kinase assays confirmed the Western Blot results and point to p38 as a potential 'clock kinase' phosphorylating Period. Taken together, these findings indicate that the p38 MAP Kinase is an integral component of the core circadian clock of Drosophila in addition to playing a role in stress-input pathways (Dusik, 2014 - Open access: 25144774).

Effects of Mutation

Misshapen acts in the Frizzled (Fz) mediated epithelial planar polarity (EPP) signaling pathway in eyes and wings. Both msn loss- and gain-of-function result in defective ommatidial polarity and wing hair formation. Genetic and biochemical analyses indicate that msn acts downstream of fz and dishevelled (dsh) in the planar polarity pathway, and thus implicates an STE20-like kinase in Fz/Dsh-mediated signaling. This demonstrates that seven-pass transmembrane receptors can signal via members of the STE20 kinase family in higher eukaryotes. Msn acts in EPP signaling through the JNK (Jun-N-terminal kinase) module as it does in dorsal closure. Although at the level of Fz/Dsh there is no apparent redundancy in this pathway, the downstream effector JNK/MAPK (mitogen-activated protein kinase) module is redundant in planar polarity generation. To address the nature of this redundancy, evidence is provided for an involvement of the related MAP kinases of the p38 subfamily in planar polarity signaling downstream of Msn (Paricio, 1999).

Although there is accumulating evidence that JNK-type MAPK modules are involved in planar polarity signaling, the analysis of mutant clones of either hep or bsk alleles shows no or weak phenotypes in imaginal discs. These observations suggest a high degree of redundancy at this level in the polarity signaling pathway. To address this issue further, a potential involvement of related kinases that could account for the proposed redundancy was examined. The recently described Drosophila kinases, belonging to the JNK/p38 class within the MAPK modules were examined for genetic interactions with the planar polarity phenotypes of sev-Dsh and sev-msn. These are obvious candidates to be cooperating with Hep and Bsk in polarity generation. At the level of Hep/JNKK (an MKK7 homolog), two other MKKs have been reported (DMKK3 and DMKK4). Similarly, at the level of Bsk/JNK, two p38-like kinases were isolated (Dp38a and Dp38b). Since no mutants have yet been isolated for these genes, whether deficiencies removing these kinases would show an interaction with sev-Dsh was examined. DMKK3 maps in the vicinity of hep: deficiencies removing DMKK3, Df(X)G24 and Df(X)H6, also remove hep. These deficiencies show externally a very strong suppression of sev-Dsh with a marked decrease of misrotated ommatidia as observed in tangential sections. Deficiency Df(3R)p13 removes the DMKK4 locus and also dominantly suppresses sev-Dsh. Similarly, deficiencies removing either Dp38a, Df(3L)crb87-4 and Df(3L)crbF89-4, or Dp38b, Df(2L)b80e3 and Df(2L)b87e25, are suppressors of sev-Dsh. Whether the respective deficiencies showed an interaction with sev>msn was also examined, and it was found that all of them act as dominant suppressors of this genotype as well. It is interesting to mention that the Msn-induced defects in rhabdomere morphology are also suppressed by those deficiencies. These interactions suggest that the p38 kinases are redundant with JNK in the context of planar polarity signaling (Paricio, 1999).

Although genetic evidence suggests an involvement of bsk (JNK) and hep (JNKK) in polarity signaling, phenotypic analyses suggest that the JNK module components are highly redundant in this process. It is interesting to note that all phenotypic defects of sev>Msn were dominantly suppressed by mutations in both components of the JNK and the p38 kinase module. In contrast to these interactions, tissue culture experiments in mammalian cells have shown that NIK overexpression leads to JNK phosphorylation, but no detectable p38 activation was observed. This difference can be explained by cell- and tissue-specific requirements, e.g. in Drosophila during dorsal closure, JNK activation downstream of Msn is not redundant, while redundancy and p38 interactions are observed in polarity signaling. Thus, it is tempting to speculate that both JNK and p38 kinases cooperate in polarity generation (Paricio, 1999).

The reported promiscuity of the kinases at both the MKK and the MAPK levels could account for the redundancy. The Drosophila MKKs and JNK/p38 MAPKs also appear to act (at least partially) on overlapping downstream targets. Whereas DMKK3 appears rather specific for p38 activation (although it activates both p38s), DMKK4 and Hep (the MKK7 cognate) both activate Bsk/JNK. Similarly, Bsk/JNK and both Dp38s can phosphorylate the downstream targets dJun and ATF2. Thus, a potential downstream target can still be phosphorylated when one of the upstream kinases is removed, and likewise for their upstream activators. An even more complicated picture may emerge when all relevant kinases are identified. Other examples of redundancy are described in yeast MAP kinases. Although KSS1 and FUS3 normally have specific roles in different pathways, it has been shown that they are redundant in the process of mating and in this case KSS1 replaces Fus3 when the latter is not present. The isolation and analysis of all the respective kinases and their mutants will be necessary to understand fully the contribution of each single kinase in planar polarity signaling (Paricio, 1999).

In vivo interaction proteomics reveal a novel p38 mitogen-activated protein kinase/Rack1 pathway regulating proteostasis in Drosophila muscle

Several recent studies suggest that systemic aging in metazoans is differentially affected by functional decline in specific tissues, such as skeletal muscle. In Drosophila, longevity appears to be tightly linked to myoproteostasis, and the formation of misfolded protein aggregates is a hallmark of senescence in aging muscle. Similarly, defective myoproteostasis is described as an important contributor to the pathology of several age-related degenerative muscle diseases in humans, e.g., inclusion body myositis. p38 mitogen-activated protein kinase (MAPK) plays a central role in a conserved signaling pathway activated by a variety of stressful stimuli. Aging p38 MAPK mutant flies display accelerated motor function decline, concomitant with an enhanced accumulation of detergent-insoluble protein aggregates in thoracic muscles. Chemical genetic experiments suggest that p38-mediated regulation of myoproteostasis is not limited to the control of reactive oxygen species production or the protein degradation pathways but also involves upstream turnover pathways, e.g., translation. Using affinity purification and mass spectrometry, this study identified Rack1 as a novel substrate of p38 MAPK in aging muscle and showed that the genetic interaction between p38b and Rack1 controls muscle aggregate formation, locomotor function, and longevity. Biochemical analyses of Rack1 in aging and stressed muscle suggest a model whereby p38 MAPK signaling causes a redistribution of Rack1 between a ribosome-bound pool and a putative translational repressor complex (Belozerov, 2014).

p38 MAP Kinase regulates circadian rhythms in Drosophila

The large repertoire of circadian rhythms in diverse organisms depends on oscillating central clock genes, input pathways for entrainment, and output pathways for controlling rhythmic behaviors. Stress-activated p38 MAP Kinases (p38K), although sparsely investigated in this context, show circadian rhythmicity in mammalian brains and are considered part of the circadian output machinery in Neurospora. This study found that Drosophila p38Kb is expressed in clock neurons, and mutants in p38Kb either are arrhythmic or have a longer free-running periodicity, especially as they age. Paradoxically, similar phenotypes are observed through either transgenic inhibition or activation of p38Kb in clock neurons, suggesting a requirement for optimal p38Kb function for normal free-running circadian rhythms. This study also found that p38Kb genetically interacts with multiple downstream targets to regulate circadian locomotor rhythms. More specifically, p38Kb interacts with the period gene to regulate period length and the strength of rhythmicity. In addition, p38Kb was shown to suppress the arrhythmic behavior associated with inhibition of a second p38Kb target, the transcription factor Mef2. Finally, manipulating p38K signaling in free-running conditions was found to alter the expression of another downstream target, MNK/Lk6, which has been shown to cycle with the clock and to play a role in regulating circadian rhythms. These data suggest that p38Kb may affect circadian locomotor rhythms through the regulation of multiple downstream pathways (Vrailas-Mortimer, 2014).


Aballay, A., et al. (2003). Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway. Curr. Biol. 13: 47-52. 12526744

Adachi-Yamada, T., et al. (1999). p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis. Mol. Cell. Biol. 19(3): 2322-9. PubMed citation: 10022918

Balakireva, M., et al. (2006). The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster. Mol Cell Biol. 26(23): 8953-63. PubMed citation: 17000765

Baldassare, J. J., Bi, Y. and Bellone, C. J. (1999). The role of p38 mitogen-activated protein kinase in IL-1 beta transcription. J. Immunol. 162(9): 5367-73. PubMed Citation: 10228013

Belozerov, V. E., Ratkovic, S., McNeill, H., Hilliker, A. J. and McDermott, J. C. (2014). In vivo interaction proteomics reveal a novel p38 mitogen-activated protein kinase/Rack1 pathway regulating proteostasis in Drosophila muscle. Mol Cell Biol 34: 474-484. PubMed ID: 24277934

Bikkavilli, R. K., Feigin, M. E. and Malbon, C. C. (2008). p38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta. J. Cell Sci. 121(Pt 21): 3598-607. PubMed Citation: 18946023

Breitwieser, W., et al. (2007). Feedback regulation of p38 activity via ATF2 is essential for survival of embryonic liver cells. Genes Dev. 21(16): 2069-82. Medline abstract: 17699753

Brook. M., et al. (2006). Posttranslational regulation of tristetraprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways. Mol. Cell Biol. 26: 2408-2418. PubMed Citation: 16508015

Campbell, D. S. and Holt, C. E. (2003). Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones. Neuron 37: 939-952. 12670423

Campbell, D. S. and Okamoto, H. (2013). Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization. J Cell Biol 203: 657-672. PubMed ID: 24385488

Cavalli, V., et al. (2001). The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI:Rab5 complex. Molec. Cell 7: 421-432. 11239470

Chang, C. I., et al. (2002). Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b. Molec. Cell 9: 1241-1249. 12086621

Cuenda, A. and Cohen, P. (1999). Stress-activated protein kinase-2/p38 and a rapamycin-sensitive pathway are required for C2C12 myogenesis. J. Biol. Chem. 274(7): 4341-6. PubMed Citation: 9933636

Davidson, S. M. and Morange, M. (2000). Hsp25 and the p38 MAPK pathway are involved in differentiation of cardiomyocytes. Dev. Biol. 218: 146-160. PubMed Citation: 10656759

Dusik, V., Senthilan, P. R., Mentzel, B., Hartlieb, H., Wulbeck, C., Yoshii, T., Raabe, T. and Helfrich-Forster, C. (2014). The MAP kinase p38 is part of Drosophila melanogaster's circadian clock. PLoS Genet 10: e1004565. PubMed ID: 25144774

Engel, F. B., et al. (2005). MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev. 19(10): 1175-87. 15870258

Engelman, J. A., Lisanti, M. P. and Scherer, P. E. (1998). Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis. J. Biol. Chem. 273(48): 32111-20

Enslen, H., Brancho, D. M. and Davis, R. J. (2000). Molecular determinants that mediate selective activation of p38 MAP kinase isoforms. EMBO J. 19: 1301-1311.

Fan, H. and Derynck, R. (1999). Ectodomain shedding of TGF-alpha and other transmembrane proteins is induced by receptor tyrosine kinase activation and MAP kinase signaling cascades. EMBO J. 18: 6962-6972.

Fan, M., et al. (2004). Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK. Genes Dev. 18: 278-289. 14744933

Fujii, R., et al. (2000). Asymmetric p38 activation in zebrafish: Its possible role in symmetric and synchronous cleavage. J. Cell Bio. 150: 1335-1348. 10995439

Fukunaga, R. and Hunter, T. (1997). MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates. EMBO J. 16(8): 1921-33

Ghatan, S., et al. (2000). p38 MAP kinase mediates Bax translocation in Nitric oxide-induced apoptosis in neurons. J. Cell Bio. 150: 335-347. 10908576

Gianni, M., et al. (2002). Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RARgamma degradation and transactivation. EMBO J. 21: 3760-3769. 12110588

Gonsalves, F. C. and Weisblat. D. A. (2007). MAPK regulation of maternal and zygotic Notch transcript stability in early development. Proc. Natl. Acad. Sci. 104(2): 531-6. PubMed citation; Online text

Hammarlund, M., Nix, P., Hauth, L., Jorgensen, E. M. and Bastiani, M. (2009). Axon regeneration requires a conserved MAP kinase pathway. Science 323(5915): 802-6. PubMed Citation: 19164707

Han, S. J., et al. (1998). Molecular cloning and characterization of a Drosophila p38 mitogen-activated protein kinase. J. Biol. Chem. 273(1): 369-74. PubMed citation: 9417090

Han, Z. S., et al. (1998). A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression. Mol. Cell. Biol. 18(6): 3527-39. PubMed citation: 9584193

Heidenreich, O., et al. (1999). MAPKAP kinase 2 phosphorylates serum response factor in vitro and in vivo. J. Biol. Chem. 274(20): 14434-43

Herskowitz, I. (1995). MAP kinase pathways in yeast: For mating and more. Cell 80: 187-197

Hida, H., et al. (1999). Regulation of mitogen-activated protein kinases by sphingolipid products in oligodendrocytes. J. Neurosci. 19(17): 7458-7467

Huang, C., et al. (1999). p38 kinase mediates UV-induced phosphorylation of p53 protein at serine 389. J. Biol. Chem. 274(18): 12229-35

Inoue, H., et al. (2001). A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK. EMBO J. 20: 5421-5430. 11574474

Inoue, H., et al. (2005). The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev. 19: 2278-2283. 16166371

Jacoby, T., et al. (1997). Two protein-tyrosine phosphatases inactivate the osmotic stress response pathway in yeast by targeting the mitogen-activated protein kinase, Hog1. J. Biol. Chem. 272(28): 17749-55

Kato, T., et al. (2003). CK2 is a c-terminal IkappaB kinase responsible for NF-kappaB activation during the UV response. Molec. Cell 12: 829-839. 14580335

Lluis, F., et al. (2005). E47 phosphorylation by p38 MAPK promotes MyoD/E47 association and muscle-specific gene transcription. EMBO J. 24: 974-984. 15719023

Ma, L. and Wang, H. Y. (2007). Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca2+ non-canonical pathway. J. Biol. Chem. 282(39): 28980-90. PubMed citation: 17684012

Macfarlane, W. M., et al. (1997). The p38/reactivating kinase mitogen-activated protein kinase cascade mediates the activation of the transcription factor insulin upstream factor 1 and insulin gene transcription by high glucose in pancreatic beta-cells. J. Biol. Chem. 272(33): 20936-44

Maekawa, M., et al. (2005). Requirement of the MAP kinase signaling pathways for mouse preimplantation development. Development 132(8): 1773-83. 15772134

Maher, P. (1999). p38 mitogen-activated protein kinase activation is required for fibroblast growth factor-2-stimulated cell proliferation but not differentiation. J. Biol. Chem. 274(25): 17491-8

Maher, P. (2001). How protein kinase C activation protects nerve cells from oxidative stress-induced cell death. J. Neurosci. 21(9): 2929-2938. 11312276

Marinissen, M. J., et al. (1999). A network of mitogen-activated protein kinases links G protein-coupled receptors to the c-jun promoter: a role for c-Jun NH2-terminal kinase, p38s, and extracellular signal-regulated kinase 5. Mol. Cell Biol. 19(6): 4289-301

Mikkola, I., et al. (1999). Phosphorylation of the transactivation domain of Pax6 by extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. J. Biol. Chem. 274(21): 15115-26

Molnar, A., et al. (1997). Cdc42Hs, but not Rac1, inhibits serum-stimulated cell cycle progression at G1/S through a mechanism requiring p38/RK. J. Biol. Chem. 272(20): 13229-35

Nadkarni, V., et al. (1999). Osmotic response element enhancer activity. Regulation through p38 kinase and mitogen-activated extracellular signal-regulated kinase kinase. J. Biol. Chem. 274(29): 20185-90

Nagata, Y., et al. (1998). Activation of p38 MAP kinase and JNK but not ERK is required for erythropoietin-induced erythroid differentiation. Blood 92(6): 1859-69. 9840233

Nakata, K., et al. (2005). Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development. Cell 120: 407-420. 15707898

O'Rourke, S. M. and Herskowitz, I. (1998). The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev. 12(18): 2874-86. PubMed Citation: 9744864

Okamoto, S.-I., et al. (2000). Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation. Proc. Natl. Acad. Sci. 97: 7561-7566. PubMed Citation: 10852968

Okamura, T., et al. (2007). ATF-2 regulates fat metabolism in Drosophila. Molec. Biol. Cell 18: 1519-1529. PubMed citation: 17314398

Ouwens, D. M., et al. (2002). Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38. EMBO J. 21: 3782-3793. 12110590

Paricio, N., et al. (1999). The Drosophila STE20-like kinase Misshapen is required downstream of the Frizzled receptor in planar polarity signaling. EMBO J. 18: 4669-4678. PubMed citation: 10469646

Penn, B. H., et al. (2004). A MyoD-generated feed-forward circuit temporally patterns gene expression during skeletal muscle differentiation. Genes Dev. 18: 2348-2353. 15466486

Pierrat, B., et al. (1998). RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38alpha mitogen-activated protein kinase (p38alphaMAPK). J. Biol. Chem. 273(45): 29661-71. PubMed Citation: 9792677

Puigserver, P., et al. (2001). Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Molec. Cell 8: 971-982. 11741533

Puri, P. L., et al. (2000). Induction of terminal differentiation by constitutive activation of p38 MAP kinase in human rhabdomyosarcoma cells. Genes Dev. 14: 574-584. PubMed Citation: 10716945

Rausch, O. and Marshall, C. J. (1999). Cooperation of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways during granulocyte colony-stimulating factor-induced hemopoietic cell proliferation. J. Biol. Chem. 274(7): 4096-105. PubMed Citation: 9933603

Reiser, V., Ruis. H. and Ammerer, G. (1999). Kinase activity-dependent nuclear export opposes stress-induced nuclear accumulation and retention of Hog1 mitogen-activated protein kinase in the budding yeast Saccharomyces cerevisiae. Mol. Biol. Cell 10(4): 1147-61. PubMed Citation: 10198063

Reynolds, T. B., et al. (1998). The high osmolarity glycerol response (HOG) MAP kinase pathway controls localization of a yeast golgi glycosyltransferase. J. Cell Biol. 143(4): 935-46. PubMed Citation: 9817752

Rolli, M., et al. (1999). Stress-induced stimulation of early growth response gene-1 by p38/Stress-activated protein kinase 2 Is mediated by a cAMP-responsive promoter element in a MAPKAP kinase 2-independent manner. J. Biol. Chem. 274(28): 19559-19564. PubMed Citation: 10391889

Sabio, G., et al. (2005). p38 gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP EMBO J. 24: 1134-1145. 15729360

Salojin, K. V., Zhang, J. and Delovitch, T. L. (1999). TCR and CD28 are coupled via ZAP-70 to the activation of the Vav/Rac-1-/PAK-1/p38 MAPK signaling pathway. J. Immunol. 163(2): 844-53. PubMed Citation: 10395678

Sano, Y., et al. (1999). ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-beta signaling. J. Biol. Chem. 274(13): 8949-57. PubMed Citation: 10085140

Sano, Y., Akimaru, H., Okamura, T., Nagao, T., Okada, M. and Ishii, S. (2005). Drosophila activating transcription factor-2 is involved in stress response via activation by p38, but not c-Jun NH(2)-terminal kinase. Mol. Biol. Cell 16: 2934-2946. PubMed citation: 15788564

Schafer, P. H., et al. (1999). p38 alpha mitogen-activated protein kinase is activated by CD28-mediated signaling and is required for IL-4 production by human CD4+CD45RO+ T cells and Th2 effector cells. J. Immunol. 162(12): 7110-9. PubMed Citation: 10358155

Seisenbacher, G., Hafen, E. and Stocker, H. (2011). MK2-dependent p38b signalling protects Drosophila hindgut enterocytes against JNK-induced apoptosis under chronic stress. PLoS Genet. 7(8): e1002168. PubMed Citation: 21829386

Sumara, G., et al. (2009). Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell 136(2): 235-48. PubMed Citation: 19135240

Tamura, K., et al. (2000). Requirement for p38alpha in erythropoietin expression: A role for stress kinases in erythropoiesis. Cell 102: 221-231. PubMed citation: 10943842

Tanoue, T., et al. (2001). Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions. EMBO J. 20: 466-479. 11157753

ter Haar, E., Prabhakar, P., Liu, X. and Lepre, C. (2007). Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer. J. Biol. Chem. 282: 9733-9739. PubMed Citation: 17255097

Thomson, S., et al. (1999). The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J. 18(17): 4779-93. PubMed Citation: 10469656

Tian, L., Chen, J., Chen, M., Gui, C., Zhong, C. Q., Hong, L., Xie, C., Wu, X., Yang, L., Ahmad, V. and Han, J. (2014). The p38 pathway regulates oxidative stress tolerance by phosphorylation of mitochondrial protein IscU. J Biol Chem [Epub ahead of print]. PubMed ID: 25204651

Vrailas-Mortimer, A. D., Ryan, S. M., Avey, M. J., Mortimer, N. T., Dowse, H. and Sanyal, S. (2014). p38 MAP Kinase regulates circadian rhythms in Drosophila. J Biol Rhythms [Epub ahead of print]. PubMed ID: 25403440

Wang, S., et al. (1999). Regulation of Rb and E2F by signal transduction cascades: divergent effects of JNK1 and p38 kinases. EMBO J. 18(6): 1559-1570. PubMed Citation: 10075927

Waskiewicz, et al. (1997). Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 16(8): 1909-20. PubMed Citation: 9155017

Winzen, R., et al. (1999). The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. 18: 4969-4980. PubMed Citation: 10487749

Xing, J., et al. (1998). Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation. Mol. Cell. Biol. 18(4): 1946-55. PubMed Citation: 9528766

Xing, H., et al. (2000). 14-3-3 proteins block apoptosis and differentially regulate MAPK cascades. EMBO J. 19: 349-358. PubMed Citation: 10654934

Xu, X., et al. (2008). Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-beta/BMP signaling during tooth and palate development. PubMed Citation: 18694570

Yang, S. H., Galanis, A. and Sharrocks, A. D. (1999). Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors. Mol. Cell. Biol. 19(6): 4028-38. PubMed Citation: 10330143

Yasuda, S., et al. (2007). Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases. Neuron 56(3): 456-71. PubMed citation: 17988630

Yu, L., Hébert, M. C. and Zhang, Y. E. (2002). TGF-ß receptor-activated p38 MAP kinase mediates Smad-independent TGF-ß responses. EMBO J. 21: 3749-3759. 12110587

Zetser, A., Gredinger, E. and Bengal E. (1999). p38 mitogen-activated protein kinase pathway promotes skeletal muscle differentiation. Participation of the Mef2c transcription factor. J. Biol. Chem. 274(8): 5193-200.

Zhang, J., et al. (1999). p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells. J. Immunol. 162(7): 3819-29. PubMed Citation: 10201899

Zhang, J., et al. (2006). Cyclic AMP inhibits p38 activation via CREB-induced Dynein light chain. Mol. Cell. Biol. 26: 1223-1234. 16449637

Zhao, M., et al. (1999). Regulation of the MEF2 family of transcription factors by p38. Mol. Cell. Biol. 19(1): 21-30. PubMed Citation: 9858528

Zuzarte-Luísa, V., et al. (2004). A new role for BMP5 during limb development acting through the synergic activation of Smad and MAPK pathways. Dev. Bio. 272: 39-52. 15242789

p38b: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology

date revised: 15 December 2014

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