Rap1 mediates sustained MAP kinase activation induced by nerve growth factor

York, Randall D.; Hong, Ying; Dillon, Tara J.; Ellig, Cindy L.; Eckert, Stephani P.; McCleskey, Edwin W.; Stork, Philip J.S.

doi:10.1038/33451

Cited by 817 publications

(748 citation statements)

References 28 publications

Supporting

Mentioning

688

Contrasting

Unclassified

Order By: Relevance

“…We find that G αi -Rap1-Src-STAT-3 pathway plays a major role in neurite outgrowth induced upon activation of a number of these receptors [102][103][104]. This is consistent with studies in PC12 cells where Rap1 and STAT-3 have been implicated [105,106]. In addition, muscarinic receptor induced neurogenesis of neural stem/progenitor cells involves CREB signaling which is mediated by Src phosphorylation [107].…”

Section: Cellular Signaling Molecules and Pathways In Neurogenesissupporting

confidence: 88%

Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways

Taylor

Fricker

Devi

et al. 2005

Cellular Signalling

144

View full text Add to dashboard Cite

Antidepressants are commonly used in the treatment of anxiety and depression, medical conditions that affect ~17-20% of the population. The clinical effects of antidepressants take several weeks to manifest, suggesting that these drugs induce adaptive changes in brain structures affected by anxiety and depression. In order to develop shorter-acting and more effective drugs for the treatment of anxiety and depression, it is important to understand how antidepressants bring about their beneficial effects. Recent reports suggest that antidepressants can induce neurogenesis in the adult brain, although the mechanisms involved are not clearly understood. In this review, we describe the different neurotransmitter systems that are affected by anxiety and depression and how they are modulated by antidepressant treatment with a focus on signaling molecules and pathways that are activated during neurotransmitter receptor induced neurogenesis.

show abstract

Section: Cellular Signaling Molecules and Pathways In Neurogenesissupporting

confidence: 88%

Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways

Taylor

Fricker

Devi

et al. 2005

Cellular Signalling

144

View full text Add to dashboard Cite

show abstract

“…In contrast, factors such as epidermal growth factor which elicit transient ERK activity are mitogenic [52]. Both epidermal growth factor and nerve growth factor induce transient ERK activation via Ras and Raf-1, but the latter can procure the sustained activation of the ERK pathway via the activation of BRaf by Rap1 [53]. This neat example of achieving a specific biological response is based on the switching of allegiances from a Ras-Raf-1 to a Rap1-B-Raf signalling complex.…”

Section: Figure 4 Multi-protein Signalling Complexesmentioning

confidence: 99%

Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions

Kölch

2000

Biochemical Journal

1,057

118

View full text Add to dashboard Cite

The Ras\Raf\MEK (mitogen-activated protein kinase\ERK kinase)\ERK (extracellular-signal-regulated kinase) pathway is at the heart of signalling networks that govern proliferation, differentiation and cell survival. Although the basic regulatory steps have been elucidated, many features of this pathway are only beginning to emerge. This review focuses on the role of protein-protein interactions in the regulation of this pathway, INTRODUCTIONThe mitogen-activated protein kinase (MAPK) pathway is one of the primordial signalling systems that Nature has used in several permutations to accomplish an amazing variety of tasks. It exists in all eukaryotes, and controls such fundamental cellular processes as proliferation, differentiation, survival and apoptosis. The basic arrangement includes a G-protein working upstream of a core module consisting of three kinases : a MAPK kinase kinase (MAPKKK) that phosphorylates and activates a MAPK kinase (MAPKK), which in turn activates MAPK ( Figure 1). This set-up provides not only for signal amplification, but, maybe even more importantly, for additional regulatory interfaces that allow the kinetics, duration and amplitude of the activity to be precisely tuned. At present we can distinguish six MAPK modules, which share structurally related components, but seem to mediate specific biological responses. For recent reviews on MAPK pathways, the reader is referred to references [1][2][3]. Here we will focus on the regulation of the ERK (extracellular-signal-regulated kinase) pathway, which features Ras as G-protein, Raf as MAPKKK, MEK (MAPK\ERK kinase) as MAPKK and ERK as MAPK.Despite enjoying a decade in the limelight of scientific interest and revealing a plethora of new insights into the circuitry of signalling pathways in general, this pathway still holds many secrets. These pertain mainly to the regulation of Raf, and to a deeper understanding of how specific biological responses are encoded by spatial and temporal changes in the activity and subcellular distribution of the pathway components, and how these fluctuations are orchestrated at the molecular level. Work from many laboratories has highlighted protein-protein interactions as powerful means of co-ordinating signalling processes, most strikingly exemplified by the assembly of multi-protein signalling complexes on activated receptors, or of transcriptionfactor complexes on gene promoters. However, it is becoming Abbreviations used : Bcr, Breakpoint cluster region ; BXB, isolated Raf-1 kinase domain ; CNK, connector-enhancer of KSR ; CK2, casein kinase 2 ; CRD, cysteine-rich domain ; DEF, docking site for ERK, FxFP ; DLK, dual leucine-zipper-bearing kinase ; ERK, extracellular-signal-regulated kinase ; Hsp, heat-shock protein ; KIM, kinase interaction motif ; IκB, inhibitor of NF-κB ; JNK, c-Jun N-terminal kinase ; KSR, kinase suppressor of Ras ; MAPK, mitogen-activated protein kinase ; MAPKK, MAPK kinase ; MAPKKK, MAPK kinase kinase ; MEK, MAPK/ERK kinase ; MEKK, MEK kinase ; MP1, MEK partner 1 ; MUK, MAPK upstream kin...

show abstract

“…Introduction cAMP inhibits cellular proliferation by interfering with the mitogen-activated protein (MAP) kinase pathway at the cytosol (Wu et al, 1993;Cook and McCormick, 1993;Burgering et al, 1993;Chen and Iyengar, 1994;Hordijk et al, 1994;York et al, 1998). The nuclear events by which cAMP exerts such growth-inhibitory e ect remain largely undetermined (Xing et al, 1996;Nakajima et al, 1996).…”

mentioning

confidence: 99%

ICER-IIγ is a tumor suppressor that mediates the antiproliferative activity of cAMP

Razavi¹,

Ramos²,

Yehia³

et al. 1998

Oncogene

View full text Add to dashboard Cite

The second messenger cAMP inhibits the proliferation of most cell types. The nuclear response of cAMP is mediated by transcription factors like the cAMPResponsive Element Modulator (CREM) gene. One of the products of the CREM gene, the transcriptional repressor Inducible cAMP Early Repressor-IIg (ICERIIg), is induced by cAMP. ICER-IIg blocks cells at the G2/M boundary of the cell cycle. Here we show that ICER-IIg dramatically inhibits the growth and DNA synthesis of mouse pituitary tumor cells and human choriocarcinoma cells. This alteration in cell growth is coupled with reduced ability of these cells to grow in an anchorage-independent manner and to form tumors in mice. These data demonstrate that ICER-IIg is a tumor suppressor gene product mediating the antiproliferative activity of cAMP.

show abstract

Rap1 mediates sustained MAP kinase activation induced by nerve growth factor

Cited by 817 publications

References 28 publications

Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways

Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways

Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions

ICER-IIγ is a tumor suppressor that mediates the antiproliferative activity of cAMP

Contact Info

Product

Resources

About