+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

C-Src signaling induced by the adapters Sin and Cas is mediated by Rap1 GTPase

C-Src signaling induced by the adapters Sin and Cas is mediated by Rap1 GTPase

Molecular & Cellular Biology 20(19): 7363-7377

Oncogenic Src proteins have been extensively studied to gain insight into the signaling mechanisms of Src. To better understand signaling through wild-type Src, we used an approach that involves activation of Src signaling through the binding of physiologic ligands to the Src SH3 domain. To this end, we used full-length and truncated versions of the multiadapter molecules Cas and Sin to activate c-Src, and we examined the intracellular pathways that mediate Src signaling under these conditions. We show that although all proteins bind to and are phosphorylated by c-Src, quantitative differences exist in the ability of the different ligands to activate c-Src signaling. In addition, we show that Sin- and Cas-induced Src signaling, as assayed by transcriptional activation, is exclusively mediated through a pathway that involves the adapter Crk and the GTP-binding protein Rap1. These data are in contrast to previous observations showing Ras to mediate signaling downstream of transforming Src alleles. In our system, we found that signaling through the oncogenic SrcY527 mutant is indeed mediated by Ras. In addition, we found that Rap1 also mediates oncogenic Src signaling. Our results show for the first time that Rap1 mediates c-Src kinase signaling and reveal mechanistic differences in the signaling properties of wild-type and transforming Src proteins.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 011664157

Download citation: RISBibTeXText

PMID: 10982853

DOI: 10.1128/mcb.20.19.7363-7377.2000

Related references

The small GTPase Rap1 is required for Mn(2+)- and antibody-induced LFA-1- and VLA-4-mediated cell adhesion. Journal of Biological Chemistry 277(33): 29468-29476, 2002

N-methyl-D-aspartate receptor-induced activation of the Rap1 GTPase is mediated by nitric oxide. Society for Neuroscience Abstracts 25(1-2): 1866, 1999

Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1. Science Signaling 5(233): Ra51-Ra51, 2012

GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2. Journal of Biological Chemistry 278(36): 34641-34653, 2003

RAP1-GTPase signaling and platelet function. Journal of Molecular Medicine 94(1): 13-19, 2016

The small GTPase Rap1 is a modulator of Hedgehog signaling. Developmental Biology 409(1): 84-94, 2016

RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase. Cancer Research 67(1): 381-390, 2007

Targets of B-cell antigen receptor signaling: the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 signaling pathway and the Rap1 GTPase. Immunological Reviews 176: 47-68, 2000

Signaling of the direction-sensing FAK/RACK1/PDE4D5 complex to the small GTPase Rap1. Small Gtpases 2(1): 54-61, 2011

Fyn is required for oxidative stress-mediated activation of Rap1 GTPase. Circulation 100(18 Suppl. ): I 409, 1999

Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron 89(3): 566-582, 2016

Thrombopoietin promotes beta1-integrin-mediated adhesion in hematopoietic cells via the small GTPase Rapl. Experimental Hematology (New York) 35(5): 793-801, 2007

Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase. Breast Cancer Research 13(2): R31, 2011

Bcr/Abl P190 interaction with Spa-1, a GTPase activating protein for the small GTPase Rap1. International Journal of Molecular Medicine 22(4): 453-458, 2008