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  1. Scaffold protein SLP-76 primes PLCγ1 for activation by ITK

    In T cells, the Tec family kinase, ITK, phosphorylates PLCγ1 at tyrosine 783 (Y783) leading to activation of phospholipase function and subsequent production of the second messengers IP 3 and DAG. In this work we demonstrate that PLCγ1 can be primed for ITK mediated phosphorylation on Y783 by a specific region of the adaptor protein, SLP-76.

  2. Tec kinases regulate T-lymphocyte development and function: new ...

    Itk functions in TCR signaling via its interactions in the LAT-SLP-76 signaling complex, where it participates in activation of PLC-γ and the downstream generation of DAG and IP 3, as well as regulation of the actin cytoskeleton via interactions with Vav.

  3. Itk: The Rheostat of the T Cell Response - PMC - PubMed Central …

    The nonreceptor tyrosine kinase Itk plays a key role in TCR-initiated signaling that directly and significantly affects the regulation of PLCγ1 and the consequent mobilization of Ca2+. Itk also participates in the regulation of cytoskeletal ...

  4. Hierarchy of signaling thresholds downstream of the T cell ... - PNAS

    Aug 27, 2021 · Interleukin-2–inducible T cell kinase (ITK) is a critical component for the optimal activation of phospholipase-C-gamma-1 (PLC-γ1), the enzyme that cleaves the membrane-embedded phosphatidylinositol bisphosphate into equimolar amounts of two second signaling messengers: inositol triphosphate (IP 3) and diacylglycerol (DAG).

  5. Conformational switches that control the TEC kinase – PLCγ …

    Jan 22, 2022 · Here, we review the current molecular level understanding of how the TEC kinases (ITK and BTK) and PLCγ1/2 are autoinhibited prior to activation of cell surface receptors, how TEC kinases are activated to specifically recognize the PLCγ substrate, and how conformational changes induced by phosphorylation trigger PLCγ activation.

  6. TEC-family kinases: regulators of T-helper-cell differentiation

    Apr 1, 2005 · Now, several studies indicate that the TEC-family kinase ITK (interleukin-2-inducible T-cell kinase) is also required for the actin reorganization and cell polarization that occurs...

  7. SLP-76 mediates and maintains activation of the Tec family kinase ITK

    Apr 17, 2007 · ITK (IL-2-inducible T cell kinase), a Tec family protein tyrosine kinase (PTK), is one of three PTKs required for T cell antigen receptor (TCR)-induced activation of phospholipase C-γ1 (PLC-γ1).

  8. Expression and Function of Tec, Itk, and Btk in Lymphocytes: …

    In functional experiments that mimic Tec up-regulation, we find that Tec overexpression in lymphocyte cell lines is sufficient to induce phospholipase Cγ (PLC-γ) phosphorylation and NFAT (nuclear factor of activated T cells) activation. In contrast, overexpression of Btk, Itk, or Bmx does not induce NFAT activation.

  9. Purification and characterization of full-length monomeric TEC …

    In this study, we have produced soluble full-length wild-type ITK protein by co-expressing an N-terminal solubility-tagged ITK construct with a kinase-specific co-chaperone CDC37 in an insect cell line.

  10. A PLC-γ1 Feedback Pathway Regulates Lck Substrate …

    Aug 8, 2017 · Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck.