Bruton's tyrosine kinase

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Bruton's tyrosine kinase
Bruton's tyrosine kinase
Belt model from BTK
Properties of human protein
Mass / length primary structure 658 amino acids
Cofactor Zn 2+
Identifier
Gene name BTK
External IDs
Enzyme classification
EC, category 2.7.10.2 tyrosine kinase
Response type Phosphorylation
Substrate GTF2I, SH3BP5, IBTK
Occurrence
Parent taxon Vertebrates

Bruton's tyrosine kinase (BTK) is an enzyme found in vertebrates that catalyzes the phosphorylation of certain proteins . It is therefore a kinase . It belongs to the tyrosine kinases of the Tec family , which is mainly expressed in B cells . BTK takes on important functions in conveying the B-cell receptor signal to the inside of the cell. A mutation in the BTK gene in humans is the cause of the so-called Bruton's syndrome ( XLA ).

construction

The Bruton tyrosine kinase consists of a PH domain at the N-terminus, followed by a TH ( Tec homology ) domain, an SH3 domain, an SH2 domain and a C-terminal kinase domain. The TH domain in turn consists of a BH domain ( Btk homology ) and one or two proline-rich regions.

activation

The first step in activating Btk is recruitment to the plasma membrane through the PH domain, which binds to phosphatidylinostiol-3,4,5-trisphosphate (PIP 3 ). PIP 3 is a product of the PI3 kinase . At the same time, the adapter protein BLNK is important for the recruitment of Btk to the membrane and thus to the B cell receptor. The activity of Btk in B cells presumably depends on the kinases Syk and Lyn .

function

An important function of Btk is the activation of the PLCγ2. Btk phosphorylates the tyrosines 753 and 759 in PLCγ2, which activates them. In addition, Btk recruits phosphatidylinositol-4-phosphate 5 kinase (PIP5K) to the plasma membrane. PIP5K in turn synthesizes the important PLCγ2 substrate phosphatitylinsitol-4,5-bisphosphate (PIP 2 ) from PIP.

A point mutation in Btk in mice means that the kinase is not directed to the plasma membrane. These mice are called Xid ( X-linked immunodeficient ) mice .

Individual evidence

  1. Orhologist at OMA
  2. a b Kurosaki T, Hikida M: Tyrosine kinases and their substrates in B lymphocytes . In: Immunol. Rev. . 228, No. 1, March 2009, pp. 132-48. doi : 10.1111 / j.1600-065X.2008.00748.x . PMID 19290925 .