Involvement of casein kinase Iϵ in cytokine-induced granulocytic differentiation

Two closely related casein kinase I (CKI) isoforms, CKIdelta and CKIepsilon, are ubiquitously expressed in many human tissues, but their specific biologic function remains to be clarified. Here, we provide the first evidence that CKIepsilon is involved in hematopoietic cell differentiation. CKIepsilon, but not CKIdelta, was down-regulated along with human granulocytic differentiation. The specific down-regulation was observed in granulocyte colony-stimulating factor (G-CSF)-induced cell differentiation of murine interleukin-3 (IL-3)-dependent myeloid progenitor 32D cells. Introduction of wild-type (WT)-CKIepsilon into 32D cells inhibited the G-CSF-induced cell differentiation, whereas kinase-negative (KN)-CKIepsilon promoted the differentiation. Neither WT- nor KN-CKIepsilon affected IL-3-dependent cell growth. Moreover, introduction of WT- or KN-CKIdelta did not affect the cytokine-induced cell growth and differentiation. While G-CSF-induced activation of signal transducers and activators of transcription 3 (STAT3) was sustained by KN-CKIepsilon, STAT3 activation was attenuated by WT-CKIepsilon. This may be explained by the fact that the suppressor of cytokine signaling 3 (SOCS3) was stabilized by its physical association with CKIepsilon. Such stabilization by CKIepsilon was also seen in IL-3-induced beta-catenin. The stabilization of downstream components of cytokine and Wnt signaling by CKIepsilon might be critical for integration of several intracellular signaling pathways to a cell-specific biologic response in hematopoietic cell self-renewal.

[1]  U. Novak,et al.  Distinct regions of the granulocyte colony-stimulating factor receptor are required for tyrosine phosphorylation of the signaling molecules JAK2, Stat3, and p42, p44MAPK. , 1995, Blood.

[2]  D. Virshup,et al.  Regulation of Casein Kinase I ε and Casein Kinase I δ by an in Vivo Futile Phosphorylation Cycle* , 1998, The Journal of Biological Chemistry.

[3]  J. Johnston,et al.  Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction1 , 2002, The Journal of Immunology.

[4]  H. Sakamoto,et al.  CIS3 and JAB have different regulatory roles in interleukin-6 mediated differentiation and STAT3 activation in M1 leukemia cells , 1998, Oncogene.

[5]  U. Knippschild,et al.  p53 is phosphorylated in vitro and in vivo by the delta and epsilon isoforms of casein kinase 1 and enhances the level of casein kinase 1 delta in response to topoisomerase-directed drugs , 1997, Oncogene.

[6]  W. Fiers,et al.  Casein Kinase-1 Phosphorylates the p75 Tumor Necrosis Factor Receptor and Negatively Regulates Tumor Necrosis Factor Signaling for Apoptosis (*) , 1995, The Journal of Biological Chemistry.

[7]  S. Frank,et al.  Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[8]  P. Graves,et al.  Role of COOH-terminal Phosphorylation in the Regulation of Casein Kinase Iδ (*) , 1995, The Journal of Biological Chemistry.

[9]  J. Johnston,et al.  Cytokine‐inducible SH2 protein‐3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N‐terminal kinase inhibitory region as well as SH2 domain , 1999, Genes to cells : devoted to molecular & cellular mechanisms.

[10]  C. Slaughter,et al.  Purification of casein kinase I and isolation of cDNAs encoding multiple casein kinase I-like enzymes. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  G. Landes,et al.  Isolation and Characterization of Human Casein Kinase Iε (CKI), a Novel Member of the CKI Gene Family (*) , 1995, The Journal of Biological Chemistry.

[12]  M. Stöter,et al.  Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus. , 2000, European journal of cell biology.

[13]  M. Hoekstra,et al.  Characterization of two protein kinases from Schizosaccharomyces pombe involved in the regulation of DNA repair. , 1994, The EMBO journal.

[14]  L. Williams,et al.  Casein kinase iepsilon in the wnt pathway: regulation of beta-catenin function. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Hagedorn,et al.  Molecular cloning, expression, and characterization of a 49-kilodalton casein kinase I isoform from rat testis. , 1993, The Journal of biological chemistry.

[16]  J. Graff,et al.  The casein kinase I family: roles in morphogenesis. , 2001, Developmental biology.

[17]  A. Ciechanover,et al.  Differential interaction of plakoglobin and β-catenin with the ubiquitin-proteasome system , 2000, Oncogene.

[18]  F. Shibasaki,et al.  Intramolecular Masking of Nuclear Import Signal on NF-AT4 by Casein Kinase I and MEKK1 , 1998, Cell.

[19]  A. Yoshimura,et al.  CIS3/SOCS-3 Suppresses Erythropoietin (EPO) Signaling by Binding the EPO Receptor and JAK2* , 2000, The Journal of Biological Chemistry.

[20]  D. Virshup,et al.  Phosphorylation and destabilization of human period I clock protein by human casein kinase Iε , 2000, Neuroreport.

[21]  P. Kelly,et al.  Inhibition and Restoration of Prolactin Signal Transduction by Suppressors of Cytokine Signaling* , 1999, The Journal of Biological Chemistry.

[22]  L. Williams,et al.  Casein kinase I « in the Wnt pathway : Regulation of b-catenin function , 1999 .

[23]  P. Coffer,et al.  Regulation of proliferation, differentiation and survival by the IL-3/IL-5/GM-CSF receptor family. , 1998, Cellular signalling.

[24]  I. Weissman,et al.  A role for Wnt signalling in self-renewal of haematopoietic stem cells , 2003, Nature.

[25]  J. Ihle.  Signaling by the cytokine receptor superfamily in normal and transformed hematopoietic cells. , 1996, Advances in cancer research.

[26]  E. J.,et al.  Distinct Regions of the Granulocyte Colony-Stimulating Factor Receptor Are Required for Tyrosine Phosphorylation of the Signaling Molecules JAK , 2002 .

[27]  L. C. Robinson,et al.  Casein kinase I gamma subfamily. Molecular cloning, expression, and characterization of three mammalian isoforms and complementation of defects in the Saccharomyces cerevisiae YCK genes. , 1995, The Journal of biological chemistry.

[28]  D. Virshup,et al.  Control of simian virus 40 DNA replication by the HeLa cell nuclear kinase casein kinase I , 1993, Molecular and cellular biology.

[29]  P. Kelly,et al.  Dual effects of suppressor of cytokine signaling (SOCS‐2) on growth hormone signal transduction , 1999, FEBS letters.

[30]  S. Rane,et al.  JAKs, STATs and Src kinases in hematopoiesis , 2002, Oncogene.

[31]  H. Endo,et al.  Thrombopoietin Regulates Bcl-xL Gene Expression through Stat5 and Phosphatidylinositol 3-Kinase Activation Pathways* , 2002, The Journal of Biological Chemistry.

[32]  P. Polakis,et al.  Axin-dependent Phosphorylation of the Adenomatous Polyposis Coli Protein Mediated by Casein Kinase 1ε* , 2001, The Journal of Biological Chemistry.

[33]  D. Virshup,et al.  Autoinhibition of Casein Kinase I ε (CKIε) Is Relieved by Protein Phosphatases and Limited Proteolysis* , 1998, The Journal of Biological Chemistry.

[34]  T. Noda,et al.  G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Michael W Young,et al.  The Drosophila Clock Gene double-time Encodes a Protein Closely Related to Human Casein Kinase Iε , 1998, Cell.

[36]  Takafumi Yoshida,et al.  The N-terminal Truncated Isoform of SOCS3 Translated from an Alternative Initiation AUG Codon under Stress Conditions Is Stable Due to the Lack of a Major Ubiquitination Site, Lys-6* , 2003, The Journal of Biological Chemistry.

[37]  J. G. Zhang,et al.  The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  D. Virshup,et al.  Casein kinase I phosphorylates and destabilizes the β-catenin degradation complex , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[39]  O. Khorkova,et al.  Human casein kinase Iδ phosphorylation of human circadian clock proteins period 1 and 2 , 2001, FEBS letters.

[40]  J. Takahashi,et al.  Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. , 2000, Science.

[41]  D. Virshup,et al.  Autoinhibition of casein kinase I epsilon (CKI epsilon) is relieved by protein phosphatases and limited proteolysis. , 1998, The Journal of biological chemistry.

[42]  R. Kelly,et al.  The AP-3 complex required for endosomal synaptic vesicle biogenesis is associated with a casein kinase Ialpha-like isoform. , 2000, Molecular biology of the cell.

[43]  S. D. Gross,et al.  The casein kinase Ialpha isoform is both physically positioned and functionally competent to regulate multiple events of mRNA metabolism. , 1999, Journal of cell science.

[44]  Donald Metcalf,et al.  SOCS3 negatively regulates IL-6 signaling in vivo , 2003, Nature Immunology.

[45]  P. Graves,et al.  Phosphate groups as substrate determinants for casein kinase I action. , 1990, The Journal of biological chemistry.

[46]  E. Eide,et al.  Nuclear Entry of the Circadian Regulator mPER1 Is Controlled by Mammalian Casein Kinase I ɛ , 2000, Molecular and Cellular Biology.

[47]  S. D. Gross,et al.  A casein kinase I isoform is required for proper cell cycle progression in the fertilized mouse oocyte. , 1997, Journal of cell science.

[48]  L. Larose,et al.  A Casein Kinase I Activity Is Constitutively Associated with Nck* , 1997, The Journal of Biological Chemistry.

[49]  L. C. Robinson,et al.  Suppressors of YCK‐encoded yeast casein kinase 1 deficiency define the four subunits of a novel clathrin AP‐like complex , 1997, The EMBO journal.

[50]  A. Tobin,et al.  Stimulus-dependent Phosphorylation of G-protein-coupled Receptors by Casein Kinase 1α* , 1997, The Journal of Biological Chemistry.

[51]  A. Miyajima,et al.  Interleukin‐3, granulocyte‐macrophage colony stimulating factor and interleukin‐5 transduce signals through two STAT5 homologs. , 1995, The EMBO journal.

[52]  D. Virshup,et al.  Casein Kinase I: From Obscurity to Center Stage , 2001, IUBMB life.

[53]  L. C. Robinson,et al.  Casein kinase I-like protein kinases encoded by YCK1 and YCK2 are required for yeast morphogenesis , 1993, Molecular and cellular biology.

[54]  H. Sakamoto,et al.  Cloning and characterization of novel CIS family genes. , 1997, Biochemical and biophysical research communications.

[55]  G. C. Johnston,et al.  Prenylated isoforms of yeast casein kinase I, including the novel Yck3p, suppress the gcs1 blockage of cell proliferation from stationary phase , 1996, Molecular and cellular biology.

[56]  J. Graff,et al.  The casein kinase I family in Wnt signaling. , 2001, Developmental biology.

[57]  S. D. Gross,et al.  Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family. , 1998, Cellular signalling.

[58]  J. Graff,et al.  Casein kinase I transduces Wnt signals , 1999, Nature.

[59]  F. Heffron,et al.  HRR25, a putative protein kinase from budding yeast: association with repair of damaged DNA , 1991, Science.

[60]  P. Coffer,et al.  Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF receptor family. , 2001, Cytokine & growth factor reviews.

[61]  Z. Fu,et al.  Relationship Between Casein Kinase I Isoforms and a Neurofilament‐Associated Kinase , 1999, Journal of neurochemistry.

[62]  S. Akira,et al.  Cis3/Socs3/Ssi3 Plays a Negative Regulatory Role in Stat3 Activation and Intestinal Inflammation , 2001, The Journal of experimental medicine.

[63]  J. Kuret,et al.  Cytoplasmic forms of fission yeast casein kinase-1 associate primarily with the particulate fraction of the cell. , 1994, The Journal of biological chemistry.

[64]  N. Iwata,et al.  Autocrine loop through cholecystokinin-B/gastrin receptors involved in growth of human leukemia cells. , 1996, Blood.

[65]  H. Matsuoka,et al.  Expression of a kinase-defective Eph-like receptor in the normal human brain. , 1997, Biochemical and biophysical research communications.

[66]  D. Hilton,et al.  SOCS Proteins: Negative Regulators of Cytokine Signaling , 2001, Stem cells.

[67]  I. Touw,et al.  Signaling mechanisms coupled to tyrosines in the granulocyte colony-stimulating factor receptor orchestrate G-CSF-induced expansion of myeloid progenitor cells. , 2003, Blood.

[68]  J. Kuret,et al.  A prenylation motif is required for plasma membrane localization and biochemical function of casein kinase I in budding yeast. , 1994, The Journal of biological chemistry.

[69]  K. Sakaguchi,et al.  Damage-mediated Phosphorylation of Human p53 Threonine 18 through a Cascade Mediated by a Casein 1-like Kinase , 2000, The Journal of Biological Chemistry.

[70]  I. Touw,et al.  Multiple Signals Mediate Proliferation, Differentiation, and Survival from the Granulocyte Colony-stimulating Factor Receptor in Myeloid 32D Cells* , 1999, The Journal of Biological Chemistry.