Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin.
Paxillin is a focal adhesion scaffolding protein which was originally identified as a substrate of the oncogenic tyrosine kinase, v-src. Paxillin has been proposed to be involved in regulation of focal adhesion dynamics. Two alternatively spliced mouse paxillin cDNAs were cloned and in the process, a paxillin-related protein, Hic-5, was also identified. Cloning and characterization of Hic-5 indicates that this protein shares extensive homology with paxillin. Although Hic-5 was originally characterized as a TGF-beta-inducible gene and proposed to be a transcription factor involved in senescence, the studies here demonstrate that Hic-5 is localized to focal adhesion in REF52 cells and can interact with the focal adhesion proteins, Fak, Frnk, and vinculin. In addition, like paxillin, Hic-5 can bind to a negative regulator of Src PTKs, csk but does not bind to the adaptor protein Crk. Like paxillin, localization of this protein to focal adhesions is mediated primarily by the LIM domains; however, sequences outside the LIM domains also play a minor role in focal adhesion targeting. These results suggest that Hic-5 like paxillin could be involved in regulation of focal adhesion dynamics and raise the possibility that Hic-5 and paxillin could have overlapping or opposing functions in the overall regulation of cell growth and differentiation.
Thomas
S M
SM
Department of Medicine, Cancer Biology Program, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215, USA. sthomas@bidmc.harvard.edu.
Hagel
M
M
Turner
C E
CE
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000081247:CSK Tyrosine-Protein Kinase; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D060588:LIM Domain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D051419:Paxillin; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016596:Vinculin / Q000378:metabolism; D019061:src-Family Kinases
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D051419:Paxillin; D010750:Phosphoproteins; C496062:Pxn protein, mouse; C090090:Tgfb1i1 protein, mouse; D016596:Vinculin; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases