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PMID: 7512969 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Contrasting roles for integrin beta 1 and beta 5 cytoplasmic domains in subcellular localization, cell proliferation, and cell migration.

The Journal of cell biology ·Vol. 125 ·No. 2 ·1994-04-00 ·Pages 447-60

Pasqualini R, Hemler ME

Abstract

To carry out a detailed comparison of the roles of integrin beta 1 and beta 5 cytoplasmic domains, we expressed both wild type beta 1 and chimeric beta 1/5 constructs in CHO cells. In the latter, the cytoplasmic domain of beta 1 was replaced with that of beta 5. The human beta 1 and beta 1/5 constructs appeared at similar levels at the cell surface (mostly as alpha 5 beta 1 heterodimers) and contributed equally to CHO cell adhesion to fibronectin. However, beta 1 but not beta 1/5 localized to focal adhesion-like structures when CHO cells were spread on fibronectin. Furthermore, only the beta 1-CHO cells showed increased proliferation in response to fibronectin plus an integrin-activating anti-beta 1 antibody, and showed increased appearance of 32P-labeled protein (p90) that correlated with proliferation. In sharp contrast, the beta 1/5-CHO cells were notably more migratory than beta 1-CHO cells in a transwell haptotactic migration assay. These results indicate that the beta 1 and beta 5 integrin subunit cytoplasmic domains can translate similar adhesive information into highly contrasting subsequent events. Thus, we have established that "inside-out" and "outside-in" integrin signaling pathways are regulated by fundamentally distinct mechanisms. In addition, we suggest that the same properties of the beta 1 cytoplasmic domain that promote recruitment to visible focal adhesion-like structures may also be conductive to cell proliferation. Conversely, the properties of the beta 5 tail that make it less likely to localize into focal adhesion-like structures may contribute to enhanced cell migration.

MeSH Terms
Amino Acid Sequence Animals CHO Cells Cell Adhesion/physiology Cell Division/physiology Cell Movement/physiology Cloning, Molecular Cricetinae Cytoplasm/physiology Fibronectins Flow Cytometry Fluorescent Antibody Technique Humans Integrin beta Chains Integrin beta1 Integrins/genetics,physiology Molecular Sequence Data Phosphoproteins/metabolism Phosphorylation Recombinant Fusion Proteins/genetics,physiology
Chemicals
Fibronectins Integrin beta Chains Integrin beta1 Integrins Phosphoproteins Recombinant Fusion Proteins integrin beta5
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pasqualini R
Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Hemler M E
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.125.2.447
Published
1994-04-00
Pages
447-60
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120033
Subset
IM
Grants
NCI NIH HHS · CA42368 · United States
External Links
PubMed source DOI: 10.1083/jcb.125.2.447 PMC Full Text View journal details
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