Lck tyrosine kinase

Ryanodin receptor p56 Lck tyrosine kinase EGF receptor Cychc nucleotide phosphodiesterase Phosphohpase A2 Ribosomal protein S6 Release of Ca Activation of T cells Growth control cAMP and cGMP metabolism Hydrolysis of phospholipids Protein biosynthesis ... 

The crystal structures of the SH2 domains of Src tyrosine kinase and Lck tyrosine kinase in complex with Tyr phosphorylated peptides have enabled important insight to be obtained into recognition of the phosphotyrosine residue and the neighboring amino acids in class lA of SH2 domains. The phosphate residue is boimd in a deep pocket of the SH2 domain, at the end of which an invariant Arg residue (Arg PB5) is located which contacts the negatively charged phosphate by a two-pronged interaction. It can be estimated that a phosphoserine or phosphothreonine residue would be too short to enter into a similar interaction with the Arg residue. 

Synaptogamin Ryanodin receptor p56 Lck tyrosine kinase EGF receptor... 

Padmanabha R, Shu Y-Z, Cook LS, Veitch JA, Donovan M, Lowe S, Huang S, Pimik D, Manly SP. 1-Methoxy-agroclavine from Penicillium sp. WC75209, a novel inhibitor of the LCK tyrosine kinase. Bioorg Med Chem Lett 8(6) 569-574, 1998. 

In spite of having no intrinsic catalytic domains, activation of T lymphocytes commences with tyrosine phosphorylations, activation of PLC-v with production of IP3 and DAG, and elevation of cytosolic free Ca2+. Thus, the consequences of receptor ligation are not dissimilar from those induced by the receptors for EGF or PDGF. An early study trying to explain the induction of tyrosine kinase activity resulted in the discovery of the nonreceptor protein tyrosine kinase Lck (p56lck), a T-cell-specific member of the Src family. Lck is associated with the cytosolic tail of CD4 (in helper T cells) or CD8 (in cytotoxic T cells) (Figure 8.14). As mentioned, the extracellular domains of these... 

The synthesis of some novel acyclonucleosides involving pyrrolo[2,3-c]pyridazine and a 4-hydroxybutyl side chain has been reported <00H(53)5>. New pyrrolo[2,3-pyrimidines containing an extended 5-substituent, as potent and selective inhibitors of lck (an src-family tyrosine kinase), have been synthesized and tested <00BMCL2171>. 

Faith A, Akdis CA, Akdis M, Simon H-U, Blaser K Defective TCR stimulation in anergized type 2 T helper cells correlates with abrogated p56(lck) and ZAP-70 tyrosine kinase activities. J Immunol 1997 159 53-60. 

Amino-3-aroylthieno[2,3-f]pytidines have been synthesized for their potential to serve as allosteric enhancers at the adenosine Aj receptor <2006BML5530>. Thieno[3,2-f]pyridine derivatives have been found to be potent Lck inhibitors that are highly selective within the Src-family of tyrosine kinases <2007BML1167>. Thieno[3,2-f]pyridine urea compounds have been shown to be potent inhibitors of KDR kinase <2007BML1246>. Thieno[2,3-/ ]pyridine-... 

Fig. 11.4. Model of signal transduction via the IL-2 receptor. Binding of IL-2 to the IL-2 receptor initiates activation of the Janus kinases Jakl and Jak3. These phosphorylate tyrosine residues in the P-chain of the IL-2 receptor and in the transcription factor StatS. SH2 domains or PTB domains of adaptor proteins can bind to the Tyr phosphate residues of the P-chain and, as shown in the figure for the Shc/Grb2/Sos complex, can transmit a signal in the direction of the Ras pathway. The phosphorylated transcription factor StatS is translocated into the nucleus and activates the transcription of corresponding gene sections. Another signaling pathway starting from the activated IL-2 receptor involves the Lck and Syk tyrosine kinases (see Chapter 8). The pathway leads to induction of genes for transcription factors such as c-Myc and c-Fos.

In addition to the Lck kinase, other tyrosine kinases are activated on ligand binding to the IL-2 receptor. These are Fyn kinase and the Janus kinases Jakl and Jak3. 

An inhibitory phosphorylation of the tyrosine kinases Lck and Fyn is also important for signal transduction, and this is performed by Csk kinase. This phosphorylation takes place at the C-terminus of Lck and inhibits the kinase activity in a similar way to that already structurally illustrated for Src kinase (see 8.3.2). 

Ilangumaran, S., Ami, S., van Echten-Deckert, G., Borisch, B., and Hoessli, D. C. (1999). Microdomain-dependent regulation of Lck and Fyn protein-tyrosine kinases in T lymphocyte plasma membranes. Mol. Biol. Cell 10(4), 891-905. 

Regarding the 1,3-diazocines, it was reported that the synthesis of the left domain of haplophytine, a hetero-dimeric alkaloid endowed with insecticidal activity, contained a pyrrolo-fused carbonyl bridged 1,3-benzodiazocine moiety <2007AG(E)4715>. It was also reported that the synthesis of a pyrazolo-fused 1,3-benzodiazocine and its activity as inhibitor of lymphocyte-specific protein tyrosine kinase (Lck) <2007W0026720>, and the thermal decomposition of a polynitro substituted 1,3-diazocine <2006RJGC499>. 

Both modes of activation are realized an example of activation by dephosphorylation is the activation of the cytoplasmic, lymphocyte tyrosine kinase (Lck) by the membrane-bound CD45-phosphatase in hemopoietic cells, whereas a release of the inhibitory... 

Src is a oncogene first found in the Rous sarcoma virus where it encodes the pp60 kinase. The corresponding cellular kinase is pp60 -s =. The Src kinases are regulated by phosphorylation de-phosphorylation. Members of the Src family of cytosolic tyrosine kinases with important funtions in cell signalling are for example Yes, Fyn, Lck, Blk, Btk, Csk, Hck, Fgr and Yrk. Fyn associates with the p85 subunit of 1-phosphatidyl inositol... 

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