pr300557m_si_005.xlsx (18.82 kB)
The Plasmodium falciparum Schizont Phosphoproteome Reveals Extensive Phosphatidylinositol and cAMP-Protein Kinase A Signaling
dataset
posted on 2012-11-02, 00:00 authored by Edwin Lasonder, Judith L. Green, Grazia Camarda, Hana Talabani, Anthony
A. Holder, Gordon Langsley, Pietro AlanoThe asexual blood stages of Plasmodium
falciparum cause the most lethal form of
human malaria. During growth within an infected red blood cell, parasite
multiplication and formation of invasive merozoites is called schizogony.
Here, we present a detailed analysis of the phosphoproteome of P. falciparum schizonts revealing 2541 unique phosphorylation
sites, including 871 novel sites. Prominent roles for cAMP-dependent
protein kinase A- and phosphatidylinositol-signaling were identified
following analysis by functional enrichment, phosphoprotein interaction
network clustering and phospho-motif identification tools. We observed
that most key enzymes in the inositol pathway are phosphorylated,
which strongly suggests additional levels of regulation and crosstalk
with other protein kinases that coregulate different biological processes.
A distinct pattern of phosphorylation of proteins involved in merozoite
egress and red blood cell invasion was noted. The analyses also revealed
that cAMP-PKA signaling is implicated in a wide variety of processes
including motility. We verified this finding experimentally using
an in vitro kinase assay and identified three novel PKA substrates
associated with the glideosome motor complex: myosin A, GAP45 and
CDPK1. Therefore, in addition to an established role for CDPK1 in
the motor complex, this study reveals the coinvolvement of PKA, further
implicating cAMP as an important regulator of host cell invasion.
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Plasmodium falciparum causeblood cell invasionphosphorylation sitesGAP 45merozoite egressProminent rolesphosphoprotein interaction network871 novel sitesimplicating cAMPprotein kinasesCDPK 1.blood cellfalciparum schizontsparasite multiplicationhost cell invasionnovel PKA substratesCDPK 1SignalingThe asexual blood stagesExtensive Phosphatidylinositolglideosome motorinositol pathwaykinase assayanalysisPlasmodium falciparum Schizont Phosphoproteome
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