Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis,
hemostasis, tissue repair,
immune response and
metastatic diffusion of tumor cells. Beta-integrins are primarily responsible for targeting integrin dimers to the appropriate subcellular locations, which in adhesive cells is mainly
focal adhesions. Integrin beta-1 mutants lose the ability to target to sites of
focal adhesions. Three novel isoforms of integrin beta-1 have been identified, termed beta-1B, beta-1C and beta-1D. Integrin beta-1B is transcribed when the proximal 26
amino acids of the
cytoplasmic domain in exon 6 are retained and then succeeded by a 12
amino acid stretch from an adjacent
intronic region. The integrin beta-1B
isoform appears to act as a dominant negative in that it inhibits cell adhesion. A second integrin beta-1
isoform, termed beta-1C, was described to have an additional 48
amino acids appended to the 26
amino acids in the
cytoplasmic domain; the function of this isoform was an inhibitory one on
DNA synthesis in the
G1 phase of the
cell cycle. The third
isoform, termed beta-1D, is a
striated muscle-specific isoform, which replaces the canonical beta-1A
isoform in
cardiac and
skeletal muscle cells. This
isoform is produced from splicing into a novel additional exon between exons 6 and 7. The
cytoplasmic domain of integrin beta-1D replaces the distal 21
amino acids (present in integrin beta-1A) with an alternative stretch of 24
amino acids (13 unique). Integrin beta-1D appears to be developmentally regulated during myofibrilogenesis, Integrin beta-1D is specifically localized to
costameres and
intercalated discs of
cardiac muscle and
costameres,
myotendinous junctions and
neuromuscular junctions of
skeletal muscle, and it appears to function in general like other integrins, as the clustering of beta-1D integrins on the surface of
CHO cells resulted in
tyrosine phosphorylation of
pp125FAK and induced
mitogen-activated protein kinase activation. ==Clinical significance==