Tec protein tyrosine kinase (TEC) (TEC)

Tec protein tyrosine kinase (TEC) is a non-receptor tyrosine kinase and the namesake member of the Tec family, which includes BTK, ITK, RLK, and BMX (UniProt P42680). It is predominantly expressed in hematopoietic cells, where it functions as a key signaling component downstream of various cell surface receptors, such as the T-cell receptor and cytokine receptors (PubMed: 24854257). TEC is involved in regulating essential cellular processes including growth, differentiation, and the immune response. In clinical oncology, TEC is recognized as a primary off-target of the irreversible BTK inhibitor ibrutinib (PubChem CID 24822711). Ibrutinib binds covalently to a conserved cysteine residue (Cys-449) in the ATP-binding pocket of TEC, leading to its inactivation. While this inhibition may contribute to the therapeutic effect in some B-cell malignancies, it is also associated with clinical adverse events. Specifically, the inhibition of TEC in platelets interferes with glycoprotein VI-mediated signaling, which can lead to an increased risk of bleeding in patients (PubMed: 25407510). Additionally, TEC inhibition has been linked to the development of atrial fibrillation, a common side effect of ibrutinib therapy. Understanding TEC's role is therefore crucial for managing the safety profile of multi-kinase inhibitors used in hematology.

Other names

Tyrosine-protein kinase TecPSCTK1TEC kinase

Irreversible covalent inhibition of the kinase domain by binding to a conserved cysteine residue (Cys-449), thereby blocking ATP binding and downstream signaling (PubMed: 24854257).