By Anthony Koleske

Abl relations Kinases in improvement and affliction presents an outline of the services of Abl relatives kinases in improvement and disorder. This new identify discusses the biochemical, genetic, and phone organic information that elucidate the mobile roles for those kinases in those methods.

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Extra resources for Abl Family Kinases in Development and Disease (Molecular Biology Intelligence Unit)

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Biological output, which would be dictated by locally available substrates and/or downstream effectors. This "partitioning" model for Abl function can accommodate the many biological functions that have been linked to Abl and explain the collection of pleiotropic and incompletely penetrant defects associated with v^^Z-knockout mice. While the idea of partitioning Abl maybe comforting, it is not satisfying. T h e selective agglomeration of the Abl functional domains in one protein, in theory, should have a higher purpose than to simply assign this tyrosine kinase to a disparate array of functions.

Cell 2002; 110(6):673-687. 7. Miranti CK, Brugge JS. Sensing the environment: a historical perspective on integrin signal transduction. Nat Cell Biol 2002; 4(4):E83-90. 8. Zamir E, Geiger B. Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 2 0 0 1 ; l l 4 ( P t 20):3583-3590. 9. Schwartz MA, Ginsberg M H . Networks and crosstalk: integrin signalling spreads. N a t Cell Biol 2002; 4(4):E65-68. 10. Nowell P C , Hungerford DA. Chromosome studies on normal and leukemic h u m a n leukocytes.

Its mutation underlies ataxiatelangiectasia (A-T)—the genetic disease predisposing to cancer. 2'^'25jhe fact that IR cannot activate the nuclear Abl tyrosine kinase in ATM-deficient cells places Abl downstream of ATM in the DNA damage signal transduction pathway. ^^ Although the Abl-Ser465Ala protein has kinase activity that is activated by cell adhesion,"^^ it is not activated by IR or cisplatin, suggesting this phosphorylation to be a general requirement for Abl activation by genotoxins. Ser465 of Abl is located in the C-lobe of the kinase domain and situated in a characteristic SQ motif that is preferentially phosphorylated by ATM and its related PIKK.

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