Tyrosine kinases plate

Thanks to crystal structures of human c-Src and its close relative, the hemopoietic cell kinase, Hck, the control of the activity of these cytosolic tyrosine kinases by phosphorylation dephosphorylation is now understood (Fig. 3.7 and Plate 5). 

Plate 2 Structure of a typical SH2 domain, bound to a phosphotyrosyl containing peptide. The SH2 domain belongs to the cytosolic pp60 sre tyrosine kinase. 

Plate 3 A view of the crystal structure of the SH3 domain of the human, cytosolic tyrosine kinase Fyn, complexed with a proline-rich SOS peptide (see ref. 35 of Chapter 3). The picture presented shows that a SH3 domain is a globular structure of approximately 60 amino acids with a well-conserved /3-sheet Structure (see ref. 36 of Chapter 3). (This picture was generously contributed by Dr Martin Noble, University of Oxford.)... 

Conventional cytogenetics, FISH, and RT-PCR have been reliably used for the laboratory detection of the t(9 22). RT-PCR detection is possible in up to 95% of cases, and may detect up to 10% of cases missed by conventional cytogenetics, and is an important modality for minimal residual disease detection. Recently, quantitative real-time PCR-based approaches have improved the ability to detect and quantify BCR-ABL transcripts in CML patients (Figure 39-15 Color Plate 4]). The recent availability the tyrosine kinase inhibitor imatinib mesylate for CML is an important development in the treatment of CML and further underscores the importance of methods for sensitive and specific identification and quantification of the BCR-ABL fusions in patients with a clinical suspicion of a CML. 

Mutations of another tyrosine kinase, FLT3, have been described in acute myeloid leukemias. The majority of these mutations are internal tandem duplications (ITDs) within the juxtamembrane domain (JMD) of the gene, and are present in up to 24% of AML cases. ITDs have been identified in all FAB subtypes of AML, most frequently in acute promyelocyticleukemia (AML FAB-M3). Figure 39-16 (Color Plate 5) shows an example of an FLT3 ITD detected by PCR... 

DeChiara, T.M. Kimble, R.B. Poueymirou, W.T. Rojas, J. Masiakowski, P. Valenzuela, D.M. Yancopoulos, G.D. Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development. Nat. Genet, 24, 271-274 (2000)... 

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