Deirdre Larkin's research while affiliated with Royal College of Surgeons in Ireland and other places
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Publications (6)
The volume-regulating protein, ICln, interacts with the conserved KxGFFKR alpha-integrin signature motif. ICln is an abundant protein (4455 +/- 650 molecules/platelet) found exclusively in the soluble cytosolic fraction of unactivated platelets. In contrast, its binding partner, the platelet integrin alpha(IIb)beta(3), is present in detergent-insol...
The major platelet integrin αIIbβ3 plays a critical role in thrombus formation and has been a major target for anti-thrombotic therapy. The precise molecular mechanism of activation of the platelet integrin αIIbβ3 is not understood although a critical role for the conserved αIIb-integrin cytoplasmic motif, KxGFFKR, has been identified. We have rece...
Resumen
La esquizofrenia se asocia con desarrolló neural alterado. Evaluamos los signos neurológicos menores (SNM) y las anomalías dermatoglíficas (recuento total de crestas a-b [RTCAB] y recuento total crestas digitales [RTCD]) en 15 pares de gemelos concordantes y dis-cordantes para esquizofrenia. Las diferencias intrapar en las puntuaciones tant...
A critical role for the conserved alpha-integrin cytoplasmic motif, KVGFFKR, is recognized in the regulation of activation of the platelet integrin alpha(IIb)beta(3). To understand the molecular mechanisms of this regulation, we sought to determine the nature of the protein interactions with this cytoplasmic motif. We used a tagged synthetic peptid...
Schizophrenia is associated with altered neural development. We assessed neurological soft signs (NSS) and dermatoglyphic anomalies (total a-b ridge count (TABRC) and total finger ridge count) in 15 pairs of twins concordant and discordant for schizophrenia. Within-pair differences in both NSS and TABRC scores were significantly greater in discorda...
The platelet integrin alphaIIbbeta3 alters conformation in response to platelet activation and ligand binding, although the molecular mechanisms involved are not known. We previously showed that a lipid modified peptide, corresponding to the membrane proximal 989KVGFFKR995 portion of the alphaIIb cytoplasmic tail, independently activates platelet a...
Citations
... It has also been suggested that elevated PDI controls integrin function and also regulates thrombin generation on binding of coagulation factors to platelet surface by feedback mechanism [23]. Enhanced levels of INTE-GRIN have also been found from 2D gel and immunoblot analysis that alters conformation in response to platelet activation [24]. Also, presence of activated platelets with increased expression of CD62P (Supporting Information Fig. 5) along with other factors in thalassemia might be held responsible for upregulation of HSP70, PDI, and INTEGRIN (Supporting Information Fig. 6 and Table 8). ...
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... ICln establishes a direct molecular interaction with the intracellular domain of α-integrin (Larkin et al., 2004(Larkin et al., , 2009Daxecker et al., 2008) (Figure 12), and perturbation of this interaction affects IClswell activation (Schedlbauer et al., 2019). Surprisingly, the interaction between the nonglycosylatable/non-phosphorylatable ICln Ser67Ala and αIIb integrin measured by FRET was stronger than the interaction between wild-type ICln and αIIb integrin ( Figure 12B). ...
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... ICln establishes a direct molecular interaction with the intracellular domain of α-integrin (Larkin et al., 2004(Larkin et al., , 2009Daxecker et al., 2008) (Figure 12), and perturbation of this interaction affects IClswell activation (Schedlbauer et al., 2019). Surprisingly, the interaction between the nonglycosylatable/non-phosphorylatable ICln Ser67Ala and αIIb integrin measured by FRET was stronger than the interaction between wild-type ICln and αIIb integrin ( Figure 12B). ...
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... NSS were also detected in siblings, but were qualitatively and quantitatively less distinct, i.e., taking an intermediate position between HC and patients. This represents a strong argument for a trait or hereditary component as backed up by the literature on patients' first-degree relatives (20), on twins (21)(22)(23)(24), and on off-spring (25)(26)(27). ...
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