MEDICAL INFORMATICS Assignment

BIOCARTA

SUBMITTED BY :ANISH JOSHI 09BIF090

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Observe how genes interact in dynamic graphical models. Our online maps depict molecular relationships from areas of active research. In an "open source" approach, this community-fed forum constantly integrates emerging proteomic information from the scientific community. It also catalogs and summarizes important resources providing information for over 120,000 genes from multiple species. Find both classical pathways as well as current suggestions for new pathways.

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Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor
Submitted by: Michael Shih, PhD. Guru:

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Interaction of T cell receptor with specific antigen in the context of MHC II activates a signal transduction pathway that leads to T cell activation. In the T cell receptor signaling pathway, the src family kinases Lck and Fyn are activated to phosphorylate proteins in the T cell receptor complex which recruit and activate the ZAP70 kinase. The activation of ZAP70 phosphorylates downstream targets that activate MAP kinase pathways and cause T cell activation. The CD45 phosphorylase also plays a role in T cell receptor signaling, dephosphorylated Lck and Fyn to activate them. Other factors modulate T cell receptor activation. Csk (COOH-terminal Srk kinase) phosphorylates Lck and deactivates it, opposing the action of CD45. The phosphorylation of Lck by Csk inhibits T cell receptor signaling and inhibits T cell activation. Csk activity is regulated in T cells by PKA, the cAMP-dependent protein kinase activated by the second messenger cAMP. The activity of Csk also appears to depend on other factors such as CBP, which recruits Csk to the plasma membrane in lipid rafts where other signaling factors such the T cell receptor complex are localized. CBP also directly activates Csk.

Chow, L.M., Fournel, M., Davidson, D., and Veillette, A. Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk. Nature 1993, 365(6442), 15660 Kawabuchi, M. et al. Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature 2000, 404(6781), 999-1003 Takeuchi, S. et al. Transmembrane phosphoprotein Cbp positively regulates the activity of the carboxyl-terminal Src kinase, Csk. J. Biol. Chem. 2000, 275(38), 29183-6 Vang, T. et al. Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor. J. Exp. Med. 2001, 193(4), 497-507