Una suerte tener al Prof Carlos Bustamante @BustamanteLab en USAL para contar su trabajo “Division of Labor and Mechanism of Translocation in a Ring ATPase” 📅Hoy 10 Abril ⏱️12pm 📍Paraninfo Universidad de Salamanca, Edif Histórico @investigausal @CICancer_com @ibfg_es @CSICCyL

Looking forward to today’s visit of Iván Plaza Menacho, who will present his work on “Structure, function and pharmacology of oncogenic protein kinases” at the @CICancer_com 29/06/23 at 12:30 cicancer.org/science-society…

Glad to establish ITC calorimetry for biomolecular interactions at CIC-IBMCC Salamanca Project lead by Carmen Guerrero Funded by Junta de Castilla y León @JCyLUniversidad #INFRARED and by European Regional Development Fund (ERDF/FEDER)🇪🇺 @investigausal @newsfrom_MP

We summarize our findings in the following multi-step mechanism of C3G activation

Binding of CrkL or CrkII to mainly P3 and secondarily to P4 stimulates the GEF activity of C3G, by favoring an open-active conformation. Phosphorylation of C3G by Src does not induce activation. Tyrosine-phosphorylation primes C3G favoring the activation by Crk proteins.

Adaptor proteins, CrkL and CrkII, are key for C3G activation. They bind through their SH3N domain to 4 Pro-rich motifs (P1-P4) of C3G with different effects. CrkL/II binding to P1-P2 mediates recruitment to the membrane but does not affect the GEF activity.

We have previously shown that the GEF activity of resting C3G is self-blocked by an intramolecular interaction of the AIR (auto-inhibitory region) and the GEF-catalytic Cdc25HD. C3G activation is about releasing the autoinhibition.

C3G (aka RapGEF1) is a guanine nucleotide exchange factor (GEF) that activates Rap1 in response to stimuli that activate tyrosine kinases.

New paper from our lab: Mechanisms of activation of C3G-Rap1 rdcu.be/c4ZKe Work done primarily by Antonio and @ArturoCarabias Great collaboration with Carmen Guerrero, Sandra Ribeiro @ProtCrys, Juan R Luque, Carlos Alfonso, Peter Schuck, et al vimeo.com/793182575

New review: Stam et al "Fetal and neonatal alloimmune thrombocytopenia" #FNAIT. Caused by alloantibodies against HPA-1a antigen in integrin beta3 Work lead by Coert Margadant with contribution from us doi.org/10.1016/j.blre.2022.… @amsterdamumc @UniLeidenNews @CICancer_com @sanquin