Ras Structure and Pathways
This web page was produced as an assignment for an undergraduate course at Davidson College.
Figure 2- This
figure is a H-Ras human G protein structure conjugated with
Diaminobenzophenone-Beta, Gamma-Imido-GTP. The crystal Ras structure
consists of 6 beta strands, 4 alpha helices, and 9 connecting loops.
The GTP, seen in the center is bound by loops L1, L2, L7, and L9 (Lewin,
1997). This figure was adapted from <http://www.ncbi.nlm.nih.gov:80/
B-cell Pathway Overview
A signal begins in the B cell when a ligand binds to the appropriate receptor. Upon binding, the B-cell receptor interacts with the Src family protein tyrosine kinases (Fyn, Blk, and Lyn). After the B-cell receptors have clustered the immunoreceptor tyrosine-based activation motifs (ITAMs) are phosphorylated in the cytoplasmic tail of Igalpha and Igbeta chains. This process forms SH2 domains and Syk binds to the Igbeta domain, which after transphosphorylation, becomes activated. The activation promotes guanine nucleotide exchange factors (GEFs) and the GEFs remove GDP and place GTP on Ras. Once Ras is activated the mitogen-activated protein kinase (MAP kinase) cascade is activated which leads to the phosphorylation and activation of the AP-1 family transcription factors, fos and jun (Janeway et al., 1999).
T-cell Pathway Overview
In T-cells, the signaling process begins when a T-cell receptor encounters a specific peptide and MHC molecule. Upon recognition of the peptide and MHC, CD4 joins with CD45, removing inhibitory phosphate groups and activating the Src-family protein kinases, Lck and Fyn. These protein kinases phosphorylate the tyrosine residue on the T-cell receptor (specifically the ITAMs of the CD3epsilon and CD3zeta chains). ZAP-70 then binds and phosphorylates LAT. LAT activates Ras with the help of Grb2 and SOS and then the MAP kinase cascade is activated. The MAP kinase cascade follows the same pathway as the B-cell (Janeway et al., 1999).
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Last Updated March 3, 1999