TIK, a novel serine/threonine kinase, is recognized by antibodies directed against phosphotyrosine

P L Icely1, P Gros, J J Bergeron

  • 1Department of Medicine, University of Ottawa, Ontario, Canada.

Insights

Researchers identified a novel serine and threonine kinase, TIK, from murine pre-B cells. This kinase, TIK, lacks typical tyrosine kinase features despite initial antibody screening.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Signaling

Background:

  • Protein kinases play crucial roles in cellular signaling pathways.
  • Tyrosine kinases are a significant class of kinases involved in cell growth and differentiation.
  • Identifying novel kinases is essential for understanding complex biological processes.

Purpose of the Study:

  • To isolate and characterize novel kinase enzymes from murine pre-B cells.
  • To identify kinases reactive to anti-phosphotyrosine antibodies.
  • To elucidate the biochemical and sequence characteristics of a newly discovered kinase.

Main Methods:

  • Screening of a lambda gt11 cDNA expression library using anti-phosphotyrosine antibodies.
  • cDNA sequencing and sequence analysis of isolated clones.
  • Biochemical assays to determine kinase activity (serine, threonine, or tyrosine).
  • Analysis of mRNA transcripts in various murine tissues.

Main Results:

  • Isolation of cDNAs encoding kinases, including the known tyrosine kinase c-lyn.
  • Characterization of a novel kinase, designated TIK.
  • Sequence analysis revealed TIK lacks conserved features of protein tyrosine kinases.
  • Biochemical assays demonstrated TIK possesses serine and threonine kinase activity, not tyrosine kinase activity.
  • The TIK protein contains a cdc2 phosphorylation consensus sequence.
  • Three TIK mRNA transcripts were detected in adult murine tissues.

Conclusions:

  • A novel serine and threonine kinase, TIK, has been identified and characterized.
  • TIK represents a new class of kinase, distinct from typical protein tyrosine kinases.
  • The presence of a cdc2 phosphorylation site suggests potential regulation by cell cycle-dependent kinases.
  • TIK is expressed in various adult murine tissues, indicating a potentially widespread biological role.

Related Concept Videos

Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: