Abstract
Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like phenotype. Structurally, Hic-5 and paxillin, a 68-kDa cytoskeletal protein, share homology such as the LD motifs in the N-terminal half and the LIM domains in the C-terminal half. Here we show that Hic-5 binds to focal adhesion kinase (FAK) by its N-terminal domain, and is localized to focal adhesions by its C-terminal LIM domains. However, Hic-5 is not tyrosine phosphorylated either by the coexpressed FAK in COS cells or by integrin stimulation in 293T cells. Furthermore, overexpression of Hic-5 results in a decreased tyrosine phosphorylation of paxillin. These findings suggest that putative functions of Hic-5 are the recruitment of FAK to focal adhesions and a competitive inhibition of tyrosine phosphorylation of paxillin.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Cell Adhesion Molecules / metabolism*
-
Cell Line
-
Cytoskeletal Proteins / metabolism*
-
DNA-Binding Proteins / metabolism*
-
Focal Adhesion Kinase 1
-
Focal Adhesion Protein-Tyrosine Kinases
-
Humans
-
Integrins / metabolism
-
Intracellular Signaling Peptides and Proteins
-
LIM Domain Proteins
-
Mice
-
Paxillin
-
Phosphoproteins / metabolism
-
Phosphorylation
-
Protein Binding
-
Protein-Tyrosine Kinases / metabolism*
-
Substrate Specificity
-
Tyrosine / metabolism
Substances
-
Cell Adhesion Molecules
-
Cytoskeletal Proteins
-
DNA-Binding Proteins
-
Integrins
-
Intracellular Signaling Peptides and Proteins
-
LIM Domain Proteins
-
PXN protein, human
-
Paxillin
-
Phosphoproteins
-
Pxn protein, mouse
-
TGFB1I1 protein, human
-
Tgfb1i1 protein, mouse
-
Tyrosine
-
Protein-Tyrosine Kinases
-
Focal Adhesion Kinase 1
-
Focal Adhesion Protein-Tyrosine Kinases
-
PTK2 protein, human
-
Ptk2 protein, mouse