Tyrosine kinase

Function

Tyrosine kinase (TK) transfers a phosphate group from ATP to tyrosine residues of proteins^[1]. TKs are classified as receptor-TK which are membrane-attached and cytoplasmic non-receptor TKs. Staurosporine inhibits TK and prevents ATP binding to it.
For Abelson tyrosine kinase see:

• Bcr-Abl and Imatinib (STI571 or Gleevec)
  
• Imatinib (Gleevec)
  
• Dasatinib (Sprycel)
  
• Nilotinib (Tasigna)
  

For Src tyrosine kinase^[2] see:

• SRC
  

For Kit tyrosine kinase (or SCF or stem cell factor) see:

• SCF-KIT
  

For Tyk tyrosine kinase see:

• Student Project 5 for UMass Chemistry 423 Spring 2015
  
• Ephrin receptors belong to the receptor tyrosine kinases.

For Focal adhesion kinase see:

• Focal adhesion kinase

See also

• Proto-oncogene tyrosine-protein kinase
  
• Tyrosine Kinase Inhibitor Pharmacokinetics
  
• Treatments:TYKI References
  
• Oncogenes & Tumor Suppressor Genes
• Cancer
• Ephrin Type-A Receptor

For references see Treatments:TYKI References.

Relevance

Bcr-Abl inhibitors are used against chronic myelogenous leukemia (CLM)^[3].

Disease

Mutated TK can cause unregulated growth of the cell and their inhibitors can be effective cancer treatment^[4].

Structural highlights

TK contains, starting from the N-terminal, SH4 – a membrane attachment domain; SH3 and SH2 domains which are a sequence-specific phosphotyrosine binding domains with roles in protein-protein interactions and the SH1 catalytic kinase domain. The of Fyn TK which contains a , in the ^[5].

Traditional Chinese medicine as dual guardians against hypertension and cancer? ^[6]

functions as a signal protein and is implicated in various diseases. The carboxyl terminal of Src kinase is important in regulating conformation and activity of Src. Src protein is locked as an inward folding conformation through binding between the phosphorylated Tyr527 and the SH2 domain under normal inactive conditions. Src is activated when dephosphorylation of Tyr527 and phosphorylation of Tyr419 occurs. From N-terminal to C-terminal, Src is composed of a (residues 270–340; colored in violet) which binds adenosine triphosphate (ATP) and a (residues 345–523; colored in green) which binds with substrates. The ATP binding site is also partially located in the larger lobe. By regulating the alpha-helix structure, the large lobe can move toward or away from the small lobe, opening or closing the cleft between the two lobes. The Src catalytic site is located within the cleft. An open conformation allows the entrance of ATP into the cleft and exit of adenosine diphosphate (ADP) from the cleft. Drugs that can either interact with the residues (404–432) on the activation loop or inhibit the activation loop from moving away and opening the cleft as a result of Tyr419 phosphorylation can effectively inhibit Src activity. In this in vivo study, and have multiple stable interactions with the two Src cleft loops while simultaneously interacting with Asp407, hindering the activation loop from activation. Considering the aforementioned interactions with Src and high affinity with EGFR, HER2, and HSP90, we suggest that Angeliferulate and HMID which both originate from the TCM Angelica sinensis may have potential as multi-targeting drug leads.

3D structures of tyrosine kinase

Tyrosine kinase 3D structures