Integrators of epidermal growth and differentiation: distinct functions for β1 and β4 integrins

doi:10.1016/S0959-437X(97)80016-0

Current Opinion in Genetics & Development

Volume 7, Issue 5, October 1997, Pages 672-682

https://doi.org/10.1016/S0959-437X(97)80016-0 Get rights and content

Abstract

Mammalian epithelia are critically dependent on interactions with components in the underlying basal lamina for proper morphogenesis and function. Substratum attachment is essential for survival, proliferation, movement, and differentiation; detachment compromises the cell's ability to perform these functions, often resulting in human disease. Interactions with the extracellular matrix are mediated through transmembrane integrin receptors that transmit signals to the cytoskeleton and to signaling molecules within the proliferating cells of the epithelium. In the past year, novel insights have emerged regarding the specific role of integrins in their attachment to extracellular matrix and in their signal transduction pathways within the epidermis.

References (64)

RO Hynes
Integrins: versatility, modulation, and signaling in cell adhesion
Cell
(1992)
J Ashkenas et al.
The extracellular matrix in epithelial biology: shared molecules and common themes in distant phyla
Dev Biol
(1996)
L Borradori et al.
Hemidesmosomes: roles in adhesion, signaling and human diseases
Curr Opin Cell Biol
(1996)
JC Adams et al.
Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human epidermal keratinocytes and nondifferentiating keratinocytes
J Cell Biol
(1991)
WG Carter et al.
Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contacts (SAC) of keratinocytes: relation to hemidesmosomes
J Cell Biol
(1990)
SH Lo et al.
Progressive kidney degeneration in mice lacking tensin
J Cell Biol
(1997)
DP Felsenfeld et al.
Ligand binding regulates the directed movement of beta1 integrins on fibroblasts
Nature
(1996)
JR Stanley
Cell adhesion molecules as targets of autoantibodies in pemphigus and pemphigoid, bullous diseases due to defective epidermal cell adhesion
Advan Immunol
(1993)
R Foisner et al.
Distribution and ultrastructure of plectin arrays in subclones of rat glioma C6 cells differing in intermediate filament protein (vimentin) expression
J Struct Biol
(1995)
E Georges-Labouesse et al.
Absence of integrin α6 leads to epidermolysis bullosa and neonatal death in mice
Nat Genet
(1996)

AM Christiano et al.

Molecular complexity of the cutaneous basement membrane zone. Revelations from the paradigms of epidermolysis bullosa

Exper Dermatol

(1996)

SB Hopkinson et al.

Molecular genetic studies of a human epidermal autoantigen (the 180-kD bullous pemphigoid antigen/BP180): identification of functionally important sequences with the BP180 molecule and evidence for an interaction between BP180 and alpha 6 integrin

J Cell Biol

(1995)

Y Poumay et al.

Basal detachment of the epidermis using dispase: tissue spatial oganization and fate of integrin alpha 6 beta 4 and hemidesmosomes

J Invest Dermatol

(1994)

CS Chen et al.

Geometric control of cell life and death

Science

(1997)

F Mainiero et al.

Signal transduction by the alpha 6 beta 4 integrin: distinct beta 4 subunit sites mediate recruitment of Shc/Grb2 and association with the cytoskeleton of hemidesmosomes

EMBO J

(1995)

SH Lo et al.

Tensin: a potential link between the cytoskeleton and signal transduction

Bioessays

(1994)

EA Clark et al.

Integrins and signal transduction pathways: the road taken

Science

(1995)

K Vuori et al.

Association of insulin receptor substrate-1 with integrins

Science

(1994)

F Mainiero et al.

The intracellular functions of α6β4 integrin are regulated by EGF

J Cell Biol

(1996)

F Mainiero et al.

The coupling of α6β4 integrin to Ras-MAP kinase pathways mediated by Shc controls keratinocyte proliferation

EMBO J

(1997)

R Juliano

Cooperation between soluble factors and integrin-mediated cell anchorage in the control of cell growth and differentiation

Bioessays

(1996)

TE O'Toole et al.

Integrin cytoplasmic domains mediate inside-out signal transduction

J Cell Biol

(1994)

Z Zhang et al.

Integrin activation by R-ras

Cell

(1996)

KK Wary et al.

The adaptor protein Shc couples a class of integrins to the control of cell cycle progression

Cell

(1996)

FM Watt et al.

Expression and function of the keratinocyte integrins

Development

(1993)

G Zambruno et al.

Transforming growth factor-beta 1 modulates beta 1 and beta 5 integrin receptors and induces the de novo expression of the alpha v beta 6 heterodimer in normal human keratinocytes: implications for wound healing

J Cell Biol

(1995)

WG Carter et al.

Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes

Cell

(1991)

MP Marinkovich et al.

The dermal-epidermal junction of human skin contains a novel laminin variant

J Cell Biol

(1992)

BE Symington et al.

Interaction of integrins alpha 3 beta 1 and alpha 2 beta 1: potential role in keratinocyte intercellular adhesion

J Cell Biol

(1993)

GO Delwel et al.

Distinct and overlapping ligand specificities of the alpha 3A beta 1 and alpha 6A beta 1 integrins: recognition of laminin isoforms

Mol Biol Cell

(1994)

PJ Jensen et al.

Beta 1 integrins do not have a major role in keratinocyte intercellular adhesion

Exp Cell Res

(1995)

LT Kim et al.

Evidence that β1 integrins in keratinocyte cell—cell junctions are not in the ligand-occupied conformation

J Invest Dermatol

(1997)

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Integrators of epidermal growth and differentiation: distinct functions for β1 and β4 integrins

Abstract

Cell

Dev Biol

Curr Opin Cell Biol

J Cell Biol

J Cell Biol

J Cell Biol

Nature

Advan Immunol

J Struct Biol

Nat Genet

Exper Dermatol

J Cell Biol

J Invest Dermatol

Science

EMBO J

Bioessays

Integrins and signal transduction pathways: the road taken

Science

Association of insulin receptor substrate-1 with integrins

Science

The intracellular functions of α6β4 integrin are regulated by EGF

J Cell Biol

The coupling of α6β4 integrin to Ras-MAP kinase pathways mediated by Shc controls keratinocyte proliferation

EMBO J

Cooperation between soluble factors and integrin-mediated cell anchorage in the control of cell growth and differentiation

Bioessays

Integrin cytoplasmic domains mediate inside-out signal transduction

J Cell Biol

Integrin activation by R-ras

Cell

The adaptor protein Shc couples a class of integrins to the control of cell cycle progression

Cell

Expression and function of the keratinocyte integrins

Development

Transforming growth factor-beta 1 modulates beta 1 and beta 5 integrin receptors and induces the de novo expression of the alpha v beta 6 heterodimer in normal human keratinocytes: implications for wound healing

J Cell Biol

Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes

Cell

The dermal-epidermal junction of human skin contains a novel laminin variant

J Cell Biol

Interaction of integrins alpha 3 beta 1 and alpha 2 beta 1: potential role in keratinocyte intercellular adhesion

J Cell Biol

Distinct and overlapping ligand specificities of the alpha 3A beta 1 and alpha 6A beta 1 integrins: recognition of laminin isoforms

Mol Biol Cell

Beta 1 integrins do not have a major role in keratinocyte intercellular adhesion

Exp Cell Res

Evidence that β1 integrins in keratinocyte cell—cell junctions are not in the ligand-occupied conformation

J Invest Dermatol