Protein kinase C α controls erythropoietin receptor signaling

被引:60
|
作者
von Lindern, M
Parren-van Amelsvoort, M
van Dijk, T
Deiner, E
van den Akker, E
van Emst-de Vries, S
Willems, P
Beug, H
Löwenberg, B
机构
[1] Erasmus Univ, Inst Hematol, NL-3000 DR Rotterdam, Netherlands
[2] Inst Mol Pathol, A-1030 Vienna, Austria
[3] Catholic Univ Nijmegen, Dept Biochem, NL-6500 HB Nijmegen, Netherlands
关键词
D O I
10.1074/jbc.M007042200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We analyzed the effect of PKC inhibitors with distinct modes of action on EpoR signaling in primary human erythroblasts and in a recently established murine erythroid cell line. Active PKC appeared essential for Epo-induced phosphorylation of the Epo receptor itself, STAT5, Gab1, Erk1/2, AKT, and other downstream targets. Under the same conditions, stem cell factor-induced signal transduction was not impaired. LY294002, a specific inhibitor of phosphoinositol 3-kinase, also suppressed Epo-induced signal transduction, which could be partially relieved by activators of PKC. PKC inhibitors or LY294002 did not affect membrane expression of the EpoR, the association of JAK2 with the EpoR, or the in vitro kinase activity of JAK2. The data suggest that PKC controls EpoR signaling instead of being a downstream effector. PKC and phosphoinositol 3-kinase may act in concert to regulate association of the EpoR complex such that it is responsive to ligand stimulation. Reduced PKC-activity inhibited Epo-dependent differentiation, although it did not effect Epo-dependent "renewal divisions" induced in the presence of Epo, stem cell factor, and dexamethasone.
引用
收藏
页码:34719 / 34727
页数:9
相关论文
共 50 条
  • [41] Protein kinase Cα is required for vanilloid receptor 1 activation -: Evidence for multiple signaling pathways
    Olah, Z
    Karai, L
    Iadarola, MJ
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (38) : 35752 - 35759
  • [42] Differential Regulation of Cysteinyl Leukotriene Receptor Signaling by Protein Kinase C in Human Mast Cells
    Kondeti, Vinay
    Duah, Ernest
    Al-Azzam, Nosayba
    Thodeti, Charles K.
    Boyce, Joshua A.
    Paruchuri, Sailaja
    PLOS ONE, 2013, 8 (08):
  • [43] High Glucose Stimulates Mineralocorticoid Receptor Transcriptional Activity Through the Protein Kinase C β Signaling
    Hayashi, Takeshi
    Shibata, Hirotaka
    Kurihara, Isao
    Yokota, Kenichi
    Mitsuishi, Yuko
    Ohashi, Kennosuke
    Murai-Takeda, Ayano
    Jo, Rie
    Ohyama, Takako
    Sakamoto, Masaya
    Tojo, Katsuyoshi
    Tajima, Naoko
    Utsunomiya, Kazunori
    Itoh, Hiroshi
    INTERNATIONAL HEART JOURNAL, 2017, 58 (05) : 794 - 802
  • [44] Protein kinase C θ is expressed in mast cells and is functionally involved in Fcε receptor I signaling
    Liu, Y
    Graham, C
    Parravicini, V
    Brown, MJ
    Rivera, J
    Shaw, S
    JOURNAL OF LEUKOCYTE BIOLOGY, 2001, 69 (05) : 831 - 840
  • [45] Protein kinase C-delta is a target of B-cell antigen receptor signaling
    Barbazuk, SM
    Gold, MR
    IMMUNOLOGY LETTERS, 1999, 69 (02) : 259 - 267
  • [46] Suppression of protein kinase C signaling by the novel isoform for bovine PGF2α receptor
    Ishii, Y
    Sakamoto, K
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 285 (01) : 1 - 8
  • [47] ACTIVATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAY BY THE ERYTHROPOIETIN RECEPTOR
    MIURA, Y
    MIURA, O
    IHLE, JN
    AOKI, N
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1994, 269 (47) : 29962 - 29969
  • [48] Protein-tyrosine Phosphatase DEP-1 Controls Receptor Tyrosine Kinase FLT3 Signaling
    Arora, Deepika
    Stopp, Sabine
    Boehmer, Sylvia-Annette
    Schons, Julia
    Godfrey, Rinesh
    Masson, Kristina
    Razumovskaya, Elena
    Ronnstrand, Lars
    Taenzer, Simone
    Bauer, Reinhard
    Boehmer, Frank-D.
    Mueller, Joerg P.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (13) : 10918 - 10929
  • [49] Activation of the vanilloid receptor by protein kinase C
    Stresow, N
    Schultz, G
    Schaefer, M
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2001, 363 (04) : R71 - R71
  • [50] Activation of erythropoietin signaling by receptor dimerization
    Watowich, SS
    INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 1999, 31 (10): : 1075 - 1088