Senena Corbalán-García

Prof. Senena Corbalán-García

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Research Focus & Metrics

Academic Career Length

34Years (1993-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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15 November 1999 in The EMBO Journal
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Núria VerdaguerNúria Verdaguer
Núria Verdaguer
SCSenena Corbalán-García
Senena Corbalán-García
WOWendy F. Ochoa
Wendy F. Ochoa
IFIgnacio Fita
Ignacio Fita
Juan Gomez-FernandezJuan Gomez-Fernandez
Juan Gomez-Fernandez
The C2 domain acts as a membrane‐targeting module in a diverse group of proteins including classical protein kinase Cs (PKCs), where it plays an essential role in activation via calcium‐dependent interactions with phosphatidylserine. The three‐dimensional structures of the Ca2+‐bound forms of the PKCα‐C2 domain both in the absence and presence of 1,2‐dicaproyl‐ sn ‐phosphatidyl‐L‐serine have now been determined by X‐ray crystallography at 2.4 and 2.6 Å resolution, respectively. In the structure of the C2 ternary complex, the glycerophosphoserine moiety of the phospholipid adopts a quasi‐cyclic conformation, with the phosphoryl group directly coordinated to one of the Ca2+ ions. Specific recognition of the phosphatidylserine is reinforced by additional hydrogen bonds and hydrophobic interactions with protein residues in the vicinity of the Ca2+ binding region. The central feature of the PKCα‐C2 domain structure is an eight‐stranded, anti‐parallel β‐barrel with a molecular topology and organization of the Ca2+ binding region closely related to that found in PKCβ‐C2, although only two Ca2+ ions have been located bound to the PKCα‐C2 domain. The structural information provided by these results suggests a membrane binding mechanism of the PKCα‐C2 domain in which calcium ions directly mediate the phosphatidylserine recognition while the calcium binding region 3 might penetrate into the phospholipid bilayer.

1 June 2014 in Biochimica et Biophysica Acta (BBA) - Biomembranes
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Journal Article
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SCSenena Corbalán-García
Senena Corbalán-García
Juan Gomez-FernandezJuan Gomez-Fernandez
Juan Gomez-Fernandez

1 October 1996 in Molecular and Cellular Biology
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SCSenena Corbalán-García
Senena Corbalán-García
SYS.-S. Yang
S.-S. Yang
KDK. R. Degenhardt
K. R. Degenhardt
DBD. Bar-Sagi
D. Bar-Sagi
The Son of sevenless proteins (Sos) are guanine nucleotide exchange factors involved in the activation of Ras by cytoplasmic and receptor tyrosine kinases. Growth factor stimulation rapidly induces the phosphorylation of Sos on multiple serine and threonine sites. Previous studies have demonstrated that growth factor-induced Sos phosphorylation occurs at the C-terminal region of the protein and is mediated, in part, by mitogen-activated protein (MAP) kinase. In this report, we describe the identification of five MAP kinase sites (S-1137, S-1167, S-1178, S-1193, and S-1197) on hSos1. We demonstrate that four of these sites, S-1132, S-1167, S-1178, and S-1193, become phosphorylated following growth factor stimulation. The MAP kinase phosphorylation sites are clustered within a region encompassing three proline-rich SH3-binding sites in the C-terminal domain of hSos1. Replacing the MAP kinase phosphorylation sites with alanine residues results in an increase in the binding affinity of Grb2 to hSos1. Interestingly, hSos2 contains only one MAP kinase phosphorylation site and, as demonstrated previously, has an increased affinity toward Grb2 compared with hSos1. These results suggest a role for MAP kinase in the regulation of Grb2-Sos interactions. Since the binding of Grb2 is important for Sos function, the phosphorylation-dependent modulation of Grb2-Sos association may provide a means of controlling Ras activation.

1 July 2006 in Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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SCSenena Corbalán-García
Senena Corbalán-García
Juan Gomez-FernandezJuan Gomez-Fernandez
Juan Gomez-Fernandez

21 April 2009 in Proceedings of the National Academy of Sciences
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MGMARTA GUERRERO-VALERO
MARTA GUERRERO-VALERO
CFCristina Ferrer-Orta
Cristina Ferrer-Orta
JQJordi Querol-Audí
Jordi Querol-Audí
CMConsuelo Marin-Vicente
Consuelo Marin-Vicente
IFIgnacio Fita
Ignacio Fita
SCSenena Corbalán-García
Senena Corbalán-García
C2 domains are widely-spread protein signaling motifs that in classical PKCs act as Ca 2+ -binding modules. However, the molecular mechanisms of their targeting process at the plasma membrane remain poorly understood. Here, the crystal structure of PKCα-C2 domain in complex with Ca 2+ , 1,2-dihexanoyl- sn -glycero-3-[phospho- l -serine] (PtdSer), and 1,2-diayl- sn -glycero-3-[phosphoinositol-4,5-bisphosphate] [PtdIns( 4 , 5 )P 2 ] shows that PtdSer binds specifically to the calcium-binding region, whereas PtdIns( 4 , 5 )P 2 occupies the concave surface of strands β3 and β4. Strikingly, the structure reveals a PtdIns( 4 , 5 )P 2 -C2 domain-binding mode in which the aromatic residues Tyr-195 and Trp-245 establish direct interactions with the phosphate moieties of the inositol ring. Mutations that abrogate Tyr-195 and Trp-245 recognition of PtdIns( 4 , 5 )P 2 severely impaired the ability of PKCα to localize to the plasma membrane. Notably, these residues are highly conserved among C2 domains of topology I, and a general mechanism of C2 domain-membrane docking mediated by PtdIns( 4 , 5 )P 2 is presented.

15 March 1997 in The EMBO Journal
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RCR.‐H. Chen
R.‐H. Chen
SCSenena Corbalán-García
Senena Corbalán-García
DBD. Bar‐Sagi
D. Bar‐Sagi
The pleckstrin homology (PH) domain is a conserved protein module present in diverse signal transducing proteins. To investigate the function of the PH domain of the Ras exchanger Sos, we have generated a recombinant (His)6‐tagged PH domain from human Sos1 (PH‐Sos). Here we show that PH‐Sos binds with high affinity(1.5 μM) to lipid vesicles containing the negatively charged phospholipid phosphatidylinositol 4,5‐bisphosphate (PIP2). When microinjected into serum‐deprived rat embryo fibroblasts or COS cells, PH‐Sos displays a homogenous subcellular distribution. However, PH‐Sos rapidly accumulates in the plasma membrane following serum stimulation and, under these conditions, is localized preferentially to the leading edge of motile cells. Surprisingly, the membrane localization of PH‐Sos is not dependent on its ability to bind PIP2. Overexpression of the PH domain of Sos has a pronounced dominant‐negative effect on serum‐induced activation of the Ras signaling pathway. These results suggest that the PH domain of Sos participates in regulating the inducible association of Sos with the membrane, and indicate the presence of specific ligands that interact with this domain to bring about the activation of Ras.