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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-6-10
pubmed:abstractText
Ras is a low molecular weight (Mr 21,000) GTP binding protein that plays an essential role in cell proliferation and differentiation. Mutations that result in constitutive activation of Ras are associated with several types of neoplastic tissue in mammals and expression of these alleles into cultured fibroblasts results in cellular transformation. Opposing the Ras activation pathway, the low molecular GTP binding protein Rap was originally observed to revert or suppress the transformed phenotype in Ki-Ras-transformed fibroblasts. This apparent antagonism between Ras and Rap function may reflect the ability of Rap and Ras to interact with the same downstream effectors, since these proteins share identical sequences within their respective effector domains. Although the precise molecular details remained to be established, there is a substantial similarity in the upstream signaling mechanisms that regulate both Ras and Rap activation. Ras GTP binding is stimulated upon the targeting of the Ras guanylnucleotide exchange factor SOS to the plasma membrane location of Ras. The carboxyl terminal domain of SOS contains a proline-rich regions that directs its association with the SH3 domains of the small adapter protein, Grb2. Similarly, the formation of active GTP-bound Rap results from the specific interaction with the Rap guanylnucleotide exchange factor C3G which specifically associates with the central SH3 domain of the small adapter protein, CrkII. Thus, efficient regulation of receptor tyrosine kinase downstream signaling events require the coordinate interplay of these two pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0918-8959
pubmed:author
pubmed:issnType
Print
pubmed:volume
46 Suppl
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S11-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Insulin and EGF receptors integrate the Ras and Rap signaling pathways.
pubmed:affiliation
Department of Physiology and Biophysics, The University of Iowa, Iowa City 52242-1109, USA.
pubmed:publicationType
Journal Article, Review