Protein tyrosine kinases translocation

Fig. 11.1 Activation of MAPK pathway by Angll and ET-1 in VSMC. Stimulation of Angll and ET-1 receptors through Gq/n activation enhances the activity of PLCp. Activated PLC 3 converts PIP2 to IP3 and diacylglycerol (DAG). IP3 elevates the concentration of intracellular calcium and DAG activates PKC. PKC and/or Ca2+/calmodulin (CaM)-dependent protein kinases (CaMK) activate nonreceptor (NR) and/or receptor (R) protein tyrosine kinases. Activation of these components signals the stimulation of Ras/Raf/MEK/ERKl/2 and p70 s6k. ERK1/2 and p70 s6k are translocated to nucleus and regulate nuclear events by activating transcription factors through phosphorylation.

Sato K, Aoto M, Mori K, Akasofu S, Tokmakov AA, Sahara S, Fukami Y. 1996. Purification and characterization of a Src-related p>57 protein-tyrosine kinase from Xenopnis oocytes. Isolation of an inactive form of the enzyme and its activation and translocation upwn fertilization. J Biol Chem 271(22) 1325C)-13257. 

Ren CL, Fu SM, Geha RS. Protein tyrosine kinase activation and protein kinase C translocation are functional components of CD40 signal transduction in resting human B cells. Immunol Invest 1994 23 437-448. 

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

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