The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 beta subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site.

Hibbs, Margaret L.; Jakes, Scott; Stacker, Steven A.; Wallace, Robert W.; Springer, Timothy A.

doi:10.1084/jem.174.5.1227

Cited by 225 publications

(145 citation statements)

References 52 publications

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“…Multiple protein kinase C and casein kinase I1 phosphorylation sites (Pinna, 1990) are also conserved at variable positions in the cytoplasmic tails. Since phosphorylation seems to influence the activity of adhesion molecules, as found for the P-subunit of CD11/CD18 integrins (Hibbs et al, 1991), the adhesive properties of the CEA subgroup members could be modulated by differential splicing within their cytoplasmic domains. Differential splicing could also affect the potential signal transduction property of CGM1, since the 'YLYL' motif, which has been shown to be associated with signal transduction (Keegan and Paul, 1992), is only present in CGMla.…”

Section: Analysis Of the Expression Pattern Of Cgmlmentioning

confidence: 99%

Genomic organization, splice variants and expression of CGM1, a CD66‐related member of the carcinoembryonic antigen gene family

Nagel

Fritz

Kuijpers

et al. 1993

European Journal of Biochemistry

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The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunoglobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGM1, a transmembrane member of the CEA family without immunoglobulin constant-like domains. CGMla and CGMlc contain cytoplasmic domains of 71 and 31 amino acids, respectively. The cytoplasmic region of CGMla is encoded by four exons (Cytl-Cyt4). Differential splicing of the Cytl exon (53 bp) leads to the formation of CGMlc. The presence or absence of potential protein kinase phosphorylation sites in the cytoplasmic domains and a sequence consensus motif involved in signal transduction in multichain immune recognition receptors indicates that this splice event is of functional importance. CGMla W A , the predominant CGMl transcript, was found in the granulocytic lineage, but not in monocytes, lymphocytes nor in a number of tumors derived from all three germ layers. Weak staining using monoclonal antibodies Tu2 and 73 in fluorescence-activated cell scan analyses indicate low concentrations of CGMl protein on the surface of granulocytes. The CGMl protein is also recognized by CD66 antibodies. Therefore, the granulocyte-specific CD66 epitope is present on at least four CEA family members: CGM1, CEA, NCA-50/90 and NCA-160.

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Section: Analysis Of the Expression Pattern Of Cgmlmentioning

confidence: 99%

Genomic organization, splice variants and expression of CGM1, a CD66‐related member of the carcinoembryonic antigen gene family

Nagel

Fritz

Kuijpers

et al. 1993

European Journal of Biochemistry

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“…In addition, phosphoamino acid analysis of CD11/18 in PMA-or FMLP-treated monocytes has revealed predominantly phosphoserine residues and only a small portion of phosphothreonine and phosphotyrosine residues (12,77). The role of phosphorylation of the integrin Mac-1 in regulating adhesion has not been established (11,32).…”

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confidence: 99%

Mac-1-dependent tyrosine phosphorylation during neutrophil adhesion

Takami

Herrera²,

Petruzzelli

2001

American Journal of Physiology-Cell Physiology

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Activated neutrophils display an array of physiological responses, including initiation of the oxidative burst, phagocytosis, and cell migration, that are associated with cellular adhesion. Under conditions that lead to cellular adhesion, we observed rapid tyrosine phosphorylation of an intracellular protein with an approximate relative molecular mass of 92 kDa (p92). Phosphorylation of p92 was inducible when Mac-1 was activated by phorbol 12-myristate 13-acetate, the β2-specific activating antibody CBR LFA-1/2, or interleukin-8 (77 amino acids). In addition, tyrosine phosphorylation of p92 was dependent on engagement of Mac-1 with ligand. Several observations suggest that this event may be an important step in the signaling pathway initiated by Mac-1 binding. p92 phosphorylation was specifically blocked with antibodies to CD11b, the α-subunit of Mac-1, and was rapidly reversible on disengagement of the integrin ligand interaction. Integrin-stimulated phosphorylation of p92 created binding sites that were recognized in vitro by the SH2 domains of c-CrkII and Src. Our observations suggest that neutrophil adhesion mediated through the binding of the β2-integrin Mac-1 initiates a signaling cascade that involves the activation of protein tyrosine kinases and leads to the regulation of protein-protein interactions via SH2 domains, a key process shared with growth factor signaling pathways.

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“…As many proteins can bind to the cytoplasmic tails of integrins and the composition of proteins bound to integrins influences the signalling pathways which integrins activate, post-translational modification of the integrin tails is a mechanism used to regulate protein binding. For example, serine/threonine phosphorylation of integrin tails by kinases, such as ERK2, AKT, protein kinase C isoforms and PDK1, can regulate the binding of adaptor proteins such as 14-3-3 isoforms and filamin to influence cell phenotypes (Freed et al 1989;Hibbs et al 1991;Kirk et al 2000;Calderwood et al 2001;Han et al 2001;Fagerholm et al 2005;Lerea et al 2007).…”

Section: Downstream Integrin Binding Partnersmentioning

confidence: 99%

Structural and mechanical functions of integrins

2013

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Integrins are ubiquitously expressed cell surface receptors that play a critical role in regulating the interaction between a cell and its microenvironment to control cell fate. These molecules are regulated either via their expression on the cell surface or through a unique bidirectional signalling mechanism. However, integrins are just the tip of the adhesome iceberg, initiating the assembly of a large range of adaptor and signalling proteins that mediate the structural and signalling functions of integrin. In this review, we summarise the structure of integrins and mechanisms by which integrin activation is controlled. The different adhesion structures formed by integrins are discussed, as well as the mechanical and structural roles integrins play during cell migration. As the function of integrin signalling can be quite varied based on cell type and context, an in depth understanding of these processes will aid our understanding of aberrant adhesion and migration, which is often associated with human pathologies such as cancer.

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The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 beta subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site.

Cited by 225 publications

References 52 publications

Genomic organization, splice variants and expression of CGM1, a CD66‐related member of the carcinoembryonic antigen gene family

Genomic organization, splice variants and expression of CGM1, a CD66‐related member of the carcinoembryonic antigen gene family

Mac-1-dependent tyrosine phosphorylation during neutrophil adhesion

Structural and mechanical functions of integrins

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