Cytoplasmic Tyrosine Kinases

Btk (Bruton s tyrosine kinase) is a phosphatidylinositol 3 -kinase sensitive cytoplasmic tyrosine kinase. Germline loss of function mutations of Btk cause X-linked agammaglobulinaemia in human and X-linked immunodeficiency in mice. 

Protein tyrosine kinases Nonreceptor tyrosine kinases Cytoplasmic tyrosine kinases Tyrosylprotein kinase Hydroxyaryl-protein kinase... 

Cytomegalovirus CMV Cytoplasmic Tyrosine Kinases Cytoskeleton Cytostatic Drugs... 

The first gene whose targeted disruption unexpectedly produced osteopetrosis was c-src (Soriano et al, 1991). c-src codes for cytoplasmic tyrosine kinase... 

Three Trks have been identified, Trk A, B and C. Ligand-binding induces Trk receptor homodimerization. This activates the intrinsic cytoplasmic tyrosine kinase activity, resulting in receptor autophosphorylation and initiation of an intracellular response. A characteristic feature of the Trk family of receptors is the presence of a leucine-rich region near the N-terminal (extracellular) end of the molecule. 

N-myristoyl o (l heteratrimeric G-proteins (a-sjbunit), see chapter S cytoplasmic tyrosine kinases, see chapter 8 N-terminus... 

In addition to receptor tyrosine kinases, the cell also contains a number of tyrosine-specific protein kinases that are not an integral component of transmembrane receptors. These nonreceptor tyrosine kinases are localized in the cytoplasm at least occasionally or they are associated with transmembrane receptors on the cytoplasmic side of the cell membrane. They are therefore also known as cytoplasmic tyrosine kinases. The nonreceptor tyrosine kinases perform essential functions in signal transduction via cytokine receptors (see Chapter 11) and T cell receptors, and in other signaling pathways. 

Permanent or transient association with subcellular structures, and variable subcellular distribution, are characteristic for the cytoplasmic tyrosine kinases. Tire nonreceptor tyrosine kinases are intracellular effector molecules that can associate with specific substrates during the process of signal transduction and activate these by tyrosine phosphorylation, to pass on the signal. Many of the functions of the nonreceptor tyrosine kinases are performed in the iimnediate vicinity of the cell membrane, whether a signal is received from an activated membrane receptor or a signal is passed on to a membrane-associated protein. 

Fig. 8.14 Domain structure of cytoplasmic tyrosine kinases. Linear representation of the domain structure of selected cytoplasmic tyrosine kinases. Details of the cytoplasmic tyrosine kinases Src 8.3.2 Jak, Tyk 11.1.5 Zap-70 11.2.2 Fak 11.3 JH Jak homology region. According to Taniguchi, (1995).

Signal transduction via the receptor-like CD 45 protein tyrosine phosphatase in cells of the blood forming system requires its intracellularly localized phosphatase activity. The cytoplasmic tyrosine kinases p56 " and p59 are thought to be cellular substrates... 

Ligand binding induces the association of the cytoplasmic tyrosine kinase with the receptor. The extracellular signal leads the tyrosine kinase to make contact with the activated receptor in this case. 

Group 2 Receptor Tyrosine Kinases and Cytoplasmic Tyrosine Kinases Receptor Tyrosine Kinases... 

JAK is a family of cytoplasmic tyrosine kinases that are associated with cytokine receptors and play a major role in the initial steps of cytokine signaling. Upon ligand binding, JAKs are activated by /ra .s-phosphorylation of two receptor-bound JAK molecules and subsequently phosphorylate a number of substrates including the cytokine receptor (D3, S3, W8). The phosphorylated receptor... 

Fig. 1. Domain architecture of ErbB receptors. ErbB receptor extracellular regions are composed of four subdomains arranged as a tandem repeat of two types of domains. Two domain nomenclatures have been proposed (Bajaj et al., 1987 Lax et al., 1988 Ward et al., 1995). The domains in order from the N-terminus are referred to as domain I (El), II (CRl), III (L2), and IV (CR2). Domains I and III are homologous domains III and IV are homologous. The extracellular region is followed by a single membrane-spanning region, a cytoplasmic tyrosine kinase, and variable length tail that harbors several phosphorylation sites.

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