Axon Regeneration Is Regulated by Ets–C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca2+ Signaling Pathways

نویسندگان

  • Chun Li
  • Naoki Hisamoto
  • Kunihiro Matsumoto
  • Kaveh Ashrafi
چکیده

The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. In Caenorhabditis elegans, the JNK and p38 MAPK pathways are important for axon regeneration. Axonal injury induces expression of the svh-2 gene encoding a receptor tyrosine kinase, stimulation of which by the SVH-1 growth factor leads to activation of the JNK pathway. Here, we identify ETS-4 and CEBP-1, related to mammalian Ets and C/EBP, respectively, as transcriptional activators of svh-2 expression following axon injury. ETS-4 and CEBP-1 function downstream of the cAMP and Ca2+-p38 MAPK pathways, respectively. We show that PKA-dependent phosphorylation of ETS-4 promotes its complex formation with CEBP-1. Furthermore, activation of both cAMP and Ca2+ signaling is required for activation of svh-2 expression. Thus, the cAMP/Ca2+ signaling pathways cooperatively activate the JNK pathway, which then promotes axon regeneration.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion

BACKGROUND We have previously shown that Matrix metalloproteinase (MMP) -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA) increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR choriocarcinoma cell-line and 6-8 w first trimester trophoblasts. METHODS The effect of Forskolin...

متن کامل

Gastrin induces c-fos gene transcription via multiple signaling pathways.

We previously observed that the trophic actions of gastrin (G17) on the AR42J rat acinar cell line are mediated by mitogen-activated protein kinase (MAPK)-induced c-fos gene transcription via protein kinase C (PKC)-dependent and -independent pathways. In this study, we further investigated the signaling pathways that target c-fos in response to G17. G17 led to a sixfold induction in luciferase ...

متن کامل

Study of PKA binding sites in cAMP-signaling pathway using structural protein-protein interaction networks

Backgroud: Protein-protein interaction, plays a key role in signal transduction in signaling pathways. Different approaches are used for prediction of these interactions including experimental and computational approaches. In conventional node-edge protein-protein interaction networks, we can only see which proteins interact but ‘structural networks’ show us how these proteins inter...

متن کامل

The scaffold protein Homer1b/c links metabotropic glutamate receptor 5 to extracellular signal-regulated protein kinase cascades in neurons.

Group I metabotropic glutamate receptors (mGluRs) increase cellular levels of inositol-1,4,5-triphosphate (IP3) and thereby trigger intracellular Ca2+ release. Also, group I mGluRs are organized with members of Homer scaffold proteins into multiprotein complexes involved in postreceptor signaling. In this study, we investigated the relative importance of the IP3/Ca2+ signaling and novel Homer p...

متن کامل

Circadian regulation of a transcription factor, ApC/EBP, in the eye of Aplysia californica.

The transcription factor, ApC/EBP (Aplysia CCAAT enhancer-binding protein) is an immediate early gene that is rapidly induced by serotonin and the cAMP signaling pathway. ApC/EBP acts as an important link following the activation of protein kinase A (PKA) in the consolidation of long-term memory in Aplysia californica. In this study, we report that levels of ApC/EBP mRNA in the eye of Aplysia a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2015