Phosphatidylinositol‐3,4,5‐trisphosphate (PtdIns‐3,4,5‐P3)/Tec kinase‐dependent calcium signaling pathway: a target for SHIP‐mediated inhibitory signals

Tec family non‐receptor tyrosine kinases have been implicated in signal transduction events initiated by cell surface receptors from a broad range of cell types, including an essential role in B‐cell development. A unique feature of several Tec members among known tyrosine kinases is the presence of an N‐terminal pleckstrin homology (PH) domain. We directly demonstrate that phosphatidylinositol‐3,4,5‐trisphosphate (PtdIns‐3,4,5‐P3) interacting with the PH domain acts as an upstream activation signal for Tec kinases, resulting in Tec kinase‐dependent phospholipase Cγ (PLCγ) tyrosine phosphorylation and inositol trisphosphate production. In addition, we show that this pathway is blocked when an SH2‐containing inositol phosphatase (SHIP)‐dependent inhibitory receptor is engaged. Together, our results suggest a general mechanism whereby PtdIns‐3,4,5‐P3 regulates receptor‐dependent calcium signals through the function of Tec kinases.

[1]  M. Negri,et al.  Activation of phospholipase Cγ by PI 3-kinase- induced PH domain-mediated membrane targeting , 1998 .

[2]  S. Rhee,et al.  Regulation of Phosphoinositide-specific Phospholipase C Isozymes* , 1997, The Journal of Biological Chemistry.

[3]  T. Hirano,et al.  Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK , 1997, Oncogene.

[4]  T. Kurosaki,et al.  Deletion of SHIP or SHP-1 Reveals Two Distinct Pathways for Inhibitory Signaling , 1997, Cell.

[5]  H. Ochs,et al.  Btk/Tec kinases regulate sustained increases in intracellular Ca2+ following B‐cell receptor activation , 1998, The EMBO journal.

[6]  A. Klippel,et al.  Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways , 1996, Molecular and cellular biology.

[7]  R. Aebersold,et al.  Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoietic cells. Association of the enzyme with various tyrosine-phosphorylated proteins. , 1994, The Journal of biological chemistry.

[8]  E. Querfurth,et al.  Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase. , 1996, The EMBO journal.

[9]  Andrius Kazlauskas,et al.  The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase , 1995, Cell.

[10]  M. Nussenzweig,et al.  A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling , 1994, Nature.

[11]  S. Volinia,et al.  Phosphatidylinositol 3-kinase: Structure and expression of the 110 kd catalytic subunit , 1992, Cell.

[12]  J. Kinet,et al.  The Emerging Field of Receptor-Mediated Inhibitory Signaling: SHP or SHIP? , 1996, Cell.

[13]  J. Fargnoli,et al.  Src family protein tyrosine kinases induce autoactivation of Bruton's tyrosine kinase , 1995, Molecular and cellular biology.

[14]  T. Kurosaki,et al.  BTK as a Mediator of Radiation-Induced Apoptosis in DT-40 Lymphoma B Cells , 1996, Science.

[15]  M. Simon,et al.  Binding of beta gamma subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  F. Alt,et al.  Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[17]  L. Cantley,et al.  Phosphoinositide kinases. , 1998, Annual review of biochemistry.

[18]  P. Tempst,et al.  Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor FeγRIIB , 1996, Nature.

[19]  R. Rickles,et al.  Identification of Itk/Tsk Src Homology 3 Domain Ligands* , 1996, The Journal of Biological Chemistry.

[20]  O. Witte,et al.  Regulation of Btk by Src family tyrosine kinases , 1996, Molecular and cellular biology.

[21]  P. Libby,et al.  PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells , 1989, Cell.

[22]  L. Stephens,et al.  Pathway of phosphatidylinositol(3,4,5)-trisphosphate synthesis in activated neutrophils , 1991, Nature.

[23]  A. Toker,et al.  Signalling through the lipid products of phosphoinositide-3-OH kinase , 1997, Nature.

[24]  G. Panayotou,et al.  Phosphoinositide 3-kinases: a conserved family of signal transducers. , 1997, Trends in biochemical sciences.

[25]  G. Mills,et al.  Activation and interaction with protein kinase C of a cytoplasmic tyrosine kinase, Itk/Tsk/Emt, on Fc epsilon RI cross-linking on mast cells. , 1995, Journal of immunology.

[26]  M. Nussenzweig,et al.  A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling , 1994, Nature.

[27]  R. Lovering,et al.  The protein product of the c-cbl protooncogene is phosphorylated after B cell receptor stimulation and binds the SH3 domain of Bruton's tyrosine kinase , 1995, The Journal of experimental medicine.

[28]  W. Fridman,et al.  Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes. , 1992, Science.

[29]  A. Hata,et al.  Genetic Evidence for a Tyrosine Kinase Cascade Preceding the Mitogen-activated Protein Kinase Cascade in Vertebrate G Protein Signaling* , 1997, The Journal of Biological Chemistry.

[30]  P. Cohen,et al.  Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα , 1997, Current Biology.

[31]  T. Kawakami,et al.  The pleckstrin homology domain of Bruton tyrosine kinase interacts with protein kinase C. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[32]  O. Witte,et al.  The Btk subfamily of cytoplasmic tyrosine kinases: structure, regulation and function. , 1995, Seminars in immunology.

[33]  P. Kiener,et al.  Co-ligation of the Antigen and Fc Receptors Gives Rise to the Selective Modulation of Intracellular Signaling in B Cells , 1997, The Journal of Biological Chemistry.

[34]  L. Cantley,et al.  Phosphatidylinositol (3,4,5)P3 interacts with SH2 domains and modulates PI 3-kinase association with tyrosine-phosphorylated proteins , 1995, Cell.

[35]  G. Klaus,et al.  Crosslinking of surface immunoglobulin and Fc receptors on B lymphocytes inhibits stimulation of inositol phospholipid breakdown via the antigen receptors , 1985, The Journal of experimental medicine.

[36]  J. Holik,et al.  Signaling by Phosphoinositide-3,4,5-Trisphosphate Through Proteins Containing Pleckstrin and Sec7 Homology Domains , 1997, Science.

[37]  J. Schlessinger,et al.  Activation of phospholipase Cγ by PI 3‐kinase‐induced PH domain‐mediated membrane targeting , 1998 .

[38]  S. P. Sidorenko,et al.  Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk , 1996, Molecular and cellular biology.

[39]  D. Pot,et al.  A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain , 1997, Molecular and cellular biology.

[40]  K. Mikoshiba,et al.  Mutation of the Pleckstrin Homology Domain of Bruton's Tyrosine Kinase in Immunodeficiency Impaired Inositol 1,3,4,5-Tetrakisphosphate Binding Capacity* , 1996, The Journal of Biological Chemistry.

[41]  S. Desiderio,et al.  The Itk/Btk/Tec family of protein-tyrosine kinases. , 1994, Chemical immunology.

[42]  L. Pike,et al.  Localization and Turnover of Phosphatidylinositol 4,5-Bisphosphate in Caveolin-enriched Membrane Domains* , 1996, The Journal of Biological Chemistry.

[43]  A. Hata,et al.  Tyrosine kinases Lyn and Syk regulate B cell receptor‐coupled Ca2+ mobilization through distinct pathways. , 1994, The EMBO journal.

[44]  Eric O Long,et al.  Negative Signaling Pathways of the Killer Cell Inhibitory Receptor and FcγRIIb1 Require Distinct Phosphatases , 1997, The Journal of experimental medicine.

[45]  D J Rawlings,et al.  Regulation of Btk function by a major autophosphorylation site within the SH3 domain. , 1996, Immunity.

[46]  F. McCormick,et al.  Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. , 1997, Science.

[47]  S. Schreiber,et al.  Regulatory intramolecular association in a tyrosine kinase of the Tec family , 1997, Nature.

[48]  P. Hawkins,et al.  Phosphatidylinositol 3-kinase-γ activates Bruton’s tyrosine kinase in concert with Src family kinases , 1997 .

[49]  L. Cantley,et al.  Identification and quantification of polyphosphoinositides produced in response to platelet-derived growth factor stimulation. , 1991, Methods in enzymology.

[50]  T. Katada,et al.  Synergistic activation of PtdIns 3-kinase by tyrosine-phosphorylated peptide and beta gamma-subunits of GTP-binding proteins. , 1996, The Biochemical journal.

[51]  H. Mano,et al.  Interleukin 3 and erythropoietin induce association of Vav with Tec kinase through Tec homology domain. , 1995, Oncogene.

[52]  T. Kurosaki,et al.  A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2 , 1996, The Journal of experimental medicine.

[53]  J. Kinet,et al.  Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering. , 1995, The EMBO journal.

[54]  M. Conley,et al.  The spectrum of mutations in Btk that cause X-linked agammaglobulinemia. , 1995, Clinical immunology and immunopathology.

[55]  S. Desiderio,et al.  BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[56]  J. Kinet,et al.  Activation of BTK by a Phosphorylation Mechanism Initiated by SRC Family Kinases , 1996, Science.

[57]  S. Desiderio,et al.  The Itk/Btk/Tec Family of Protein-Tyrosine Kinases , 1994 .

[58]  M. Harnett,et al.  Analysis of signaling via surface immunoglobulin receptors on b cells from cba/n mice , 1989, European journal of immunology.

[59]  David R. Kaplan,et al.  Direct Regulation of the Akt Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate , 1997, Science.

[60]  L. Cantley,et al.  A Comparative Analysis of the Phosphoinositide Binding Specificity of Pleckstrin Homology Domains* , 1997, The Journal of Biological Chemistry.

[61]  J. Cambier,et al.  Fc gammaRIIB1 inhibition of BCR-mediated phosphoinositide hydrolysis and Ca2+ mobilization is integrated by CD19 dephosphorylation. , 1997, Immunity.

[62]  R. Aebersold,et al.  Both phosphatidylinositol 3-kinase and phosphatidylinositol 4-kinase products are increased by antigen receptor signaling in B cells. , 1994, Journal of immunology.

[63]  W. Fantl,et al.  Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase. , 1995, Science.