Jm. Baisden et al., The actin filament-associated protein AFAP-110 is an adaptor protein that modulates changes in actin filament integrity, ONCOGENE, 20(44), 2001, pp. 6435-6447
The actin filament-associated protein of 110 kDa (AFAP-110) was first ident
ified as an SH3/SH2 binding partner for the nonreceptor tyrosine kinase, Sr
c. Subsequent data have demonstrated that AFAP-110 can interact with other
Src family members. AFAP-110 contains additional protein binding modules in
cluding two pleckstrin homology domains, a leucine zipper motif and a targe
t sequence for serine/threonine phosphorylation. AFAP-110 interacts with ac
tin filaments directly via a carboxy terminal actin-binding domain. Thus AF
AP-110 may function as an adaptor protein by linking Src family members and
/or other signaling proteins to actin filaments. AFAP-110 also has an intri
nsic capability to alter actin filament integrity that can be revealed upon
conformational changes associated with phosphorylation or mutagenesis. Rec
ent data has indicated that AFAP-110 may also serve to activate cSrc in res
ponse to this conformational change as well. Thus, AFAP-110 may function in
several ways by (1) acting as an adaptor protein that links signaling mole
cules to actin filaments, (2) serving as a platform for the construction of
larger signaling complexes, (3) serving as an activator of Src family kina
ses in response to cellular signals that alter its conformation and (4) dir
ectly effecting actin filament organization as an actin filament cross-link
ing protein. Here, we will review the structure and function of AFAP-110 as
well as potential binding partners and effectors of AFAP-110's ability to
alter actin filament integrity.