Mary Zutter
Faculty Member
Last active: 4/26/2016

Role of the alpha1 and alpha2 integrin cytoplasmic domains in cell morphology, motility and responsiveness to stimulation by the protein kinase C pathway.

Wang H, Gai Q, Yang X, Li Z, Linders B, Santoro SA, Zutter MM
Cell Adhes Commun. 2000 7 (4): 281-97

PMID: 10714390

The alpha1beta1 and alpha2beta1 integrins, extracellular matrix receptors for collagens and/or laminins, have similarities in structure and ligand binding. Recent studies suggest that the two receptors mediate distinct post-ligand binding events and are not simply redundant receptors. To discern the mechanisms by which the two receptors differ, we focused on the roles of the cytoplasmic domains of the alpha subunits. We expressed either full-length alpha1 integrin subunit cDNA (X1C1), full-length alpha2 integrin subunit cDNA (X2C2), chimeric cDNA composed of the extracellular and transmembrane domains of alpha2 subunit and the cytoplasmic domain of alpha1 (X2C1), chimeric cDNA composed of the extracellular and transmembrane domains of alpha1 subunit and the cytoplasmic domain of alpha2 (X1C2), alpha1 cDNA truncated after the GFFKR sequence (X1C0) or alpha2 cDNA truncated after the GFFKR sequence (X2C0) in K562 cells. Although the cytoplasmic domains of the alpha1 and alpha2 subunits were not required for adhesion, the extent of adhesion at low substrate density was enhanced by the presence of either the alpha1 or alpha2 cytoplasmic tail. Spreading was also influenced by the presence of an alpha subunit cytoplasmic tail. Activation of the protein kinase C pathway with phorbol dibutyrate-stimulated motility that was dependent upon the presence of the alpha2 cytoplasmic tail. Both the phosphatidylinosotide-3-OH kinase and the mitogen-activated protein kinase pathways were required for phorbol-activated, alpha2-cytoplasmic tail-dependent migration.

MeSH Terms (21)

Antigens, CD Cell Adhesion Cell Movement Cell Size Collagen Cytoplasm DNA, Complementary Flow Cytometry Gene Expression Hematopoietic Stem Cells Humans Integrin alpha1 Integrin alpha2 Integrins K562 Cells MAP Kinase Signaling System Phosphatidylinositol 3-Kinases Protein Kinase C Protein Structure, Tertiary Receptors, Collagen Recombinant Fusion Proteins

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