HIC-5: A Mobile Molecular Scaffold Regulating the Anchorage Dependence of Cell Growth

Figure 1

The paxillin/focal adhesion-associated adaptor protein family; domain structure and binding factors. The paxillin family includes HIC-5, Leupaxin, which is preferentially expressed in hematopoietic cells, and PaxB, an orthologue of paxillin in the slime mould Dictyostellium discoidium. The family members share many of their structural characteristics and binding factors. They have four to five leucine-rich motifs (LD repeats) in the N-terminal half and four cysteine-rich regions composed of two zinc fingers (LIM domains) in the C-terminal half. These domains mediate the protein-protein interactions that allow paxillin to bind a variety of structural and signalling molecules, such as the structural protein vinculin, the SH2-SH3 adaptor protein Crk, Src, focal adhesion kinase (FAK), PTK2B protein tyrosine kinase 2 beta (PYK2), a negative regulator of Src, the Csk nonreceptor tyrosine kinase, the G protein-coupled receptor kinase interactor Arf GAP1 (GIT-1), paxillin-kinase linker (PKL), protein tyrosine phosphatase-PEST (PTP-PEST), and heat shock protein 27 (HSP27). The LIM domains also mediate the localization of Hic-5 at the nucleus and at focal adhesions. HIC-5 has the same binding partners, except for Crk and Src, as paxillin.