The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors

Structural Basis for Asymmetric Association of the βPIX Coiled Coil and Shank PDZ

“…5,13,17,18 GIT and PIX proteins are tightly associated as a multimeric complex capable of linking important signaling molecules, including PAKs. 3,18 PIX and GITs colocalize at focal complexes, the cell periphery, and cytoplasmic complexes. 19,20 Oligomerization by the CC domains appears to be essential for specific subcellular localizations since mutations that disrupt PIX oligomerization cause it to be diffusely distributed in the cytoplasm.…”

“…The C-terminal portion of PIX interacts with the Spa2 homology domain of GITs (Gprotein-coupled receptor kinase interacting proteins), and the PIX SH3 domain associates with a proline-rich sequence in PAK (p21-activated kinase), thereby forming a large GIT-PIX-PAK heteromolecular complex. 3 αPIX is distinguished from most βPIX isoforms by the presence of a calponin homology domain. 4 At their C-terminal ends, both αPIX and β1PIX contain a coiled-coil (CC) domain, whereas the corresponding region of β2PIX is serine rich.…”

Structures of Dimeric GIT1 and Trimeric β-PIX and Implications for GIT–PIX Complex Assembly

“…9 These results were taken as an indication that the complex contains multiple copies of each oligomer. In contrast, our data show that one GIT1 dimer (170 kDa) interacts with one β-PIX trimer (220 kDa) to form a heteropentameric complex with a calculated molecular mass of 390 kDa.…”

“…24 GIT proteins contribute to the regulation of such cellular processes as cell adhesion and endocytic trafficking by acting as scaffolding proteins that promote the formation of multiprotein assemblies. Like PIX proteins, they contain a predicted CC region that mediates homodimerization and heterodimerization between GIT1 and GIT2 8,9,[25][26][27] (Fig. 1).…”

“…8,28,29 At focal adhesions, association of GIT1 and β-PIX with additional proteins, such as Pak and FAK, can occur. 2,8,9,27,30,31 Although the importance of the GIT PIX complex as a scaffold for the formation of multiprotein assemblies is well established, there is only limited knowledge about the precise composition of such complexes and their mode of interaction. To gain a better understanding of the regulatory mechanisms that govern the formation of these assemblies, we have characterized the molecular determinants of GIT1-β-PIX complex formation.…”