Development tyrosine phosphorylation

Tyrosine phosphorylation is involved in every stage of neuronal development 426... 

Tyrosine phosphorylation plays a role in virtually every step in the development and functions of a neuron, including survival and differentiation, the extension of axons to their targets and synapse formation and function (Fig. 24-11) (see Chs 25, 27, 28 and 30). Because of the plethora of effects of tyrosine phosphorylation on neuronal function, the following is by no means a comprehensive review but focuses on several examples that demonstrate its significance for the nervous system (Fig. 24-11). 

In comparison to the level of cellular serine or threonine phosphorylation, protein tyrosine phosphorylation occurs at quite low levels in normal cells but dramatically increases upon oncogenic transformation or stimulation. Since the first discovery in 1978 that the transforming protein from Rous sarcoma virus (pp60vsrc) exhibited intrinsic kinase activity/5 protein kinase activity has also been shown to be inherent to other growth factor receptors such as epidermal growth factor receptor and the insulin receptor,[6 91 and to involve autophosphorylation processes. The diverse biochemical activity exhibited by protein tyrosine phosphorylation has stimulated the development of chemical methods for the preparation of phosphorylated peptides for use as substrates in elucidating the biochemical and physiological activity of phosphorylated site(s). 

Friese, M. B., Blagden, C. S. and Burden, S. J. (2007) Synaptic differentiation is defective in mice lacking acetylcholine receptor beta-subunit tyrosine phosphorylation. Development 134,4167-4 176. 

Integrin betal null platelets from conditional knockout mice develop normally, platelet count is normal. Collagen induced platelet aggregation is delayed but otherwise normal tyrosine phosphorylation pattern is normal but phosphorylation is delayed. Bleeding time in bone marrow chimeric mice is normal no major in vivo defects (Nieswandt et al. 2001). 

Brequinar (DUP 785, NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis by inhibiting dihydro-orotate dehydrogenase. It was originally developed as an anticancer drug, but has also been investigated for its immunosuppressant activity after transplantation. Some data suggest that that the immunosuppressant activity of brequinar may be partly due to inhibition of tyrosine phosphorylation in lymphocytes (1). 

RNP-based fluorescent probes would be ideal to detect protein tyrosine phosphorylation directly in the solution. To develop a fluorescent RNP sensor for the pTyr residue, RNP receptors has been developed for the pTyr residue.57 RNP receptors for pTyr were isolated from a pool of RNA sequences (430) as described... 

Visconti, P.E., Bailey, J.L., Moore, G.D., Pan, D., Olds-Clarke, P., and Kopf, G.S. (1995a). Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development f2i l 129-1137. 

Visconti, P.E., Moore, G.D., Bailey, J.L., Leclerc, P., Connors, S.A., Pan, D., Olds-Clarke, P., and Kopf, G.S. (1995b). Capacitation of mouse spermatozoa. 11. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development I21 1139-1150. Visconti, P.E., Johnson, L., Oyaski, M., Pomes, M., Moss, S.B., Gerton, G.L., and Kopf. G.S. (1997). Regulation, localization, and anchoring of protein kinase A subunits during mouse sperm capacitation. Dev. Biol. 792 351-363. 

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