Molecular cloning, expression and evolutionary analysis of the avian tyrosine kinase JAK1

P Bartunek1, N P Koritschoner, D Brett

  • 1Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle Strasse 10, D-13092, Berlin, Germany.

Gene
|April 27, 1999
PubMed

Insights

Researchers cloned and sequenced chicken JAK1, revealing its conserved structure and ubiquitous expression, particularly in lymphoid cells. This finding deepens our understanding of cytokine receptor signaling pathways.

Area of Science:

  • Molecular Biology
  • Immunology
  • Biochemistry

Background:

  • Janus protein tyrosine kinases (JAK) are crucial for cytokine receptor signaling.
  • Understanding JAK family evolution and function across species is vital.

Purpose of the Study:

  • To clone and characterize the chicken homologue of JAK1.
  • To investigate the structural conservation and expression patterns of chicken JAK1.

Main Methods:

  • cDNA cloning and nucleotide sequencing of chicken JAK1.
  • Phylogenetic analysis and amino acid sequence identity comparisons.
  • Southern hybridization and mRNA expression analysis in various tissues.

Main Results:

  • Chicken JAK1 cDNA sequence determined, encoding a 133kDa protein with conserved JAK homology (JH1-JH7) domains.
  • Phylogenetic analysis shows chicken JAK1 is most related to mammalian JAK1 (80% human, 79% mouse identity).
  • Ubiquitous expression of a 5.5kb JAK1 mRNA observed, with highest levels in lymphoid cells.

Conclusions:

  • Chicken JAK1 shares significant structural and sequence homology with mammalian JAK1, particularly in kinase domains.
  • The conserved nature of JAK1 suggests a fundamental role in vertebrate signaling pathways.
  • Ubiquitous expression highlights JAK1's broad involvement in cellular functions, especially immune responses.

Related Concept Videos

In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...