title: Central role of PI3K-SYK interaction in fibrinogen-induced lamellipodia and filopodia formation in platelets.
abstract: The WAVE complex-1, a complex of WAVE, Abi1, NAP1, PIR121, HSPC300, RacGTP and Arp2/3 proteins, and WASP complex-1, a complex of WASP, Cdc42, PIP2, and Arp2/3 proteins, are involved in lamellipodia and filopodia formation, respectively. It is known that the two complexes have opposite dynamics. Furthermore, Rac has two guanine nucleotide exchange factors, Vav and Sos, whose role in activating Rac is not well understood. In this work, by the construction of signaling network, analysis, and mathematical modeling, I show that Sos generates a pulse of WAVE complex-1, decreasing the response time of WAVE complex-1 formation upon the stimulation of platelets by fibrinogen. Furthermore, I also show that the dynamics of WAVE and WASP complexes depends on PI3K-SYK interaction. In the absence of this interaction, the WAVE complex-1 does not form and the WASP complex-1 remains at the initial, sustained level. Thus, I show the significance of the two protein/protein complexes: Sos and PI3K-SYK interaction, in fibrinogen-induced lamellipodia and filopodia formation in platelets.
authors.affiliation: Department of Chemical Engineering Indian Institute of Technology Kanpur India.
authors.forename: Raghvendra
authors.initials: R
authors.lastname: Singh
keywords: Sos; WASP; WAVE; filopodia; lamellipodia; response time