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Title: Signal transduction involving p21-activated kinase
Keywords: focal complexes, oligomerisation, ArfGAP, PAK activation, GIT1 phosphorylation, PIX
Issue Date: 12-May-2004
Citation: LOO TSUI HAN (2004-05-12). Signal transduction involving p21-activated kinase. ScholarBank@NUS Repository.
Abstract: GIT1,PIX and PAK are components of a protein complex implicated in Rho GTPases signalling to actin cytoskeleton and focal complex rearrangements; GIT1 protein complex is enriched at these focal complexes. Structural analysis shows that GIT1a??s leucine zipper domain mediates oligomerisation and this function is auto-inhibited. Oligomerisation of GIT1 increases its binding to PIX which is necessary for targeting to focal complexes, thereby recruiting PAK. Besides this, GIT1 through its amino-terminus ArfGAP domain also drives PAK activation in a Rho GTPases independent manner. Thus within the protein complex, GIT1 and PIX confer both localisation and activation cues for PAK. This is particularly relevant to PAK signalling since constitutively active PAK has been shown to re-organise actin cytoskeleton and focal complexes. Furthermore, active PAK phosphorylates GIT1 and is probably responsible for GIT1 protein complex turnover at focal complex. Similarly a novel GIT1-PKA interaction might acts in a similar manner as PAK to down-regulate GIT1 protein complex signalling.
Appears in Collections:Ph.D Theses (Open)

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