PMID: 17913496 Ligand binding and receptor clustering leads to phosphorylation of these tyrosines by Src-family tyrosine kinases.

PMID: 17913496, 7541794, 17086186, 9351824 Similar results were later obtained using beta1 or beta2 integrin-mediated activation of human monocytic cell lines [11] or primary murine macrophages [8] and [12], and beta2 integrin-dependent activation of human neutrophils [13] as well as in CHO cells heterologously expressing the alphaIIb and beta3 integrin subunits and Syk.

PMID: 17913496, 7541794, 17086186, 9351824 Similar results were later obtained using beta1 or beta2 integrin-mediated activation of human monocytic cell lines [11] or primary murine macrophages [8] and [12], and beta2 integrin-dependent activation of human neutrophils [13] as well as in CHO cells heterologously expressing the alphaIIb and beta3 integrin subunits and Syk.

PMID: 17913496, 10689303, 10781399 The phospho-ITAM then recruits the Syk or the related ZAP-70 tyrosine kinase through their dual phosphotyrosine-binding SH2 domains, leading to their phosphorylation and activation, which in turn initiates further downstream signaling. PMID: 17913496, 17086186, 10547366, 11940607 Src-family kinases are indeed involved in integrin-mediated responses, including Syk phosphorylation, in neutrophils [8], [20] and [28], macrophages [12] and [29] and platelets.

PMID: 17913496, 7541794, 17086186, 9351824 Similar results were later obtained using beta1 or beta2 integrin-mediated activation of human monocytic cell lines [11] or primary murine macrophages [8] and [12], and beta2 integrin-dependent activation of human neutrophils [13] as well as in CHO cells heterologously expressing the alphaIIb and beta3 integrin subunits and Syk.

PMID: 17913496, 7541794, 17086186, 9351824 Similar results were later obtained using beta1 or beta2 integrin-mediated activation of human monocytic cell lines [11] or primary murine macrophages [8] and [12], and beta2 integrin-dependent activation of human neutrophils [13] as well as in CHO cells heterologously expressing the alphaIIb and beta3 integrin subunits and Syk.

PMID: 17913496, 10689303, 10781399 The phospho-ITAM then recruits the Syk or the related ZAP-70 tyrosine kinase through their dual phosphotyrosine-binding SH2 domains, leading to their phosphorylation and activation, which in turn initiates further downstream signaling. PMID: 17913496, 17086186, 10547366, 11940607 Src-family kinases are indeed involved in integrin-mediated responses, including Syk phosphorylation, in neutrophils [8], [20] and [28], macrophages [12] and [29] and platelets.

PMID: 17913496, 17086186, 11672534 These studies revealed that Syk is required for beta2 integrin-mediated spreading and extracellular signal-regulated protein kinase (ERK) activation in macrophages [8] and [19] , various integrin-mediated functional and signaling responses of neutrophils [20], as well as alphaIIb/beta3 integrin-mediated spreading and concomitant downstream signaling in platelets. PMID: 17913496, 17086186 The two ITAM-bearing adapters are also required for beta2 integrin-induced activation of ERK in macrophages with a predominant role for DAP12 in these cells.

PMID: 17913496 Later studies suggested that this ITAM-independent Syk activation occurs through the direct binding of Syk to integrin beta-chains.

PMID: 17913496, 16943434, 17086186, 17353363 Unexpectedly, three recent reports using genetically modified mice indicate that beta2 and beta3 integrins, which do not share structural similarity with classical immunoreceptors, also signal by an ITAM-based, immunoreceptor-like mechanism in several different primary cell types. PMID: 17913496, 16943434, 17086186 The ITAM-mediated signaling model proposes that integrins activate Syk through Src-family mediated phosphorylation of the ITAM tyrosines within transmembrane adapters (DAP12 and FcR¦Ã) possibly through association with yet unidentified immunoreceptor-like molecules, followed by recruitment of Syk via its tandem SH2 domains [7] and 8[8] PY, phosphotyrosine.

PMID: 17913496, 16943434, 17086186, 17353363 Unexpectedly, three recent reports using genetically modified mice indicate that beta2 and beta3 integrins, which do not share structural similarity with classical immunoreceptors, also signal by an ITAM-based, immunoreceptor-like mechanism in several different primary cell types. PMID: 17913496, 16943434, 17086186 The ITAM-mediated signaling model proposes that integrins activate Syk through Src-family mediated phosphorylation of the ITAM tyrosines within transmembrane adapters (DAP12 and FcR¦Ã) possibly through association with yet unidentified immunoreceptor-like molecules, followed by recruitment of Syk via its tandem SH2 domains [7] and 8[8] PY, phosphotyrosine.

PMID: 17913496, 7541794, 17086186, 9351824 Similar results were later obtained using beta1 or beta2 integrin-mediated activation of human monocytic cell lines [11] or primary murine macrophages [8] and [12], and beta2 integrin-dependent activation of human neutrophils [13] as well as in CHO cells heterologously expressing the alphaIIb and beta3 integrin subunits and Syk. PMID: 17913496, 16943434, 17086186, 17353363 Unexpectedly, three recent reports using genetically modified mice indicate that beta2 and beta3 integrins, which do not share structural similarity with classical immunoreceptors, also signal by an ITAM-based, immunoreceptor-like mechanism in several different primary cell types.

PMID: 17913496 Later studies suggested that this ITAM-independent Syk activation occurs through the direct binding of Syk to integrin beta-chains.

PMID: 17913496, 17086186 Integrin-mediated adhesion of neutrophils leads to phosphorylation of DAP12 and FcRgamma by Src-family kinases and their association with the Syk SH2 domains [8]. DAP12 and/or FcRgamma are also required for adhesion-induced Syk phosphorylation in neutrophils and macrophages. PMID: 17913496 DAP12, FcRgamma and all known DAP12- and FcRgamma-associated molecules contain a charged residue within their membrane-spanning region (Box 2). These residues probably form intramembrane salt bridges that stabilize the receptor?adapter complex.

PMID: 17913496, 17086186 Integrin-mediated adhesion of neutrophils leads to phosphorylation of DAP12 and FcRgamma by Src-family kinases and their association with the Syk SH2 domains [8]. DAP12 and/or FcRgamma are also required for adhesion-induced Syk phosphorylation in neutrophils and macrophages.

PMID: 17913496, 17086186 Integrin-mediated adhesion of neutrophils leads to phosphorylation of DAP12 and FcRgamma by Src-family kinases and their association with the Syk SH2 domains [8]. DAP12 and/or FcRgamma are also required for adhesion-induced Syk phosphorylation in neutrophils and macrophages.

PMID: 17913496, 17086186 Integrin-mediated adhesion of neutrophils leads to phosphorylation of DAP12 and FcRgamma by Src-family kinases and their association with the Syk SH2 domains [8]. DAP12 and/or FcRgamma are also required for adhesion-induced Syk phosphorylation in neutrophils and macrophages.

PMID: 17913496, 17086186 Integrin-mediated adhesion of neutrophils leads to phosphorylation of DAP12 and FcRgamma by Src-family kinases and their association with the Syk SH2 domains [8]. DAP12 and/or FcRgamma are also required for adhesion-induced Syk phosphorylation in neutrophils and macrophages.

PMID: 17913496, 10689303, 10781399 The phospho-ITAM then recruits the Syk or the related ZAP-70 tyrosine kinase through their dual phosphotyrosine-binding SH2 domains, leading to their phosphorylation and activation, which in turn initiates further downstream signaling.

PMID: 17913496, 10689303, 10781399 The phospho-ITAM then recruits the Syk or the related ZAP-70 tyrosine kinase through their dual phosphotyrosine-binding SH2 domains, leading to their phosphorylation and activation, which in turn initiates further downstream signaling.

PMID: 17913496, 10689303, 10781399 The phospho-ITAM then recruits the Syk or the related ZAP-70 tyrosine kinase through their dual phosphotyrosine-binding SH2 domains, leading to their phosphorylation and activation, which in turn initiates further downstream signaling.

PMID: 17913496, 10689303, 10781399 The phospho-ITAM then recruits the Syk or the related ZAP-70 tyrosine kinase through their dual phosphotyrosine-binding SH2 domains, leading to their phosphorylation and activation, which in turn initiates further downstream signaling.

PMID: 17913496, 7541794, 17086186, 9351824 Similar results were later obtained using beta1 or beta2 integrin-mediated activation of human monocytic cell lines [11] or primary murine macrophages [8] and [12], and beta2 integrin-dependent activation of human neutrophils [13] as well as in CHO cells heterologously expressing the alphaIIb and beta3 integrin subunits and Syk. PMID: 17913496, 16943434, 17086186, 17353363 Unexpectedly, three recent reports using genetically modified mice indicate that beta2 and beta3 integrins, which do not share structural similarity with classical immunoreceptors, also signal by an ITAM-based, immunoreceptor-like mechanism in several different primary cell types.

PMID: 17913496, 17086186, 11672534 These studies revealed that Syk is required for beta2 integrin-mediated spreading and extracellular signal-regulated protein kinase (ERK) activation in macrophages [8] and [19] , various integrin-mediated functional and signaling responses of neutrophils [20], as well as alphaIIb/beta3 integrin-mediated spreading and concomitant downstream signaling in platelets. PMID: 17913496, 17086186 The two ITAM-bearing adapters are also required for beta2 integrin-induced activation of ERK in macrophages with a predominant role for DAP12 in these cells.

PMID: 17913496 Hence, DAP12 and FcRgamma are required for osteoclast development and function, possibly as a result of their role in alphaV/beta3 integrin signal transduction.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496, 15249579 Later studies, however, revealed that Vav1 and Vav3 have a critical but overlapping role in neutrophil activation by beta2-integrins.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496 Ligand binding and receptor clustering leads to phosphorylation of these tyrosines by Src-family tyrosine kinases.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.

PMID: 17913496 Activation of these kinases leads to downstream signaling, such as phosphorylation of SLP-76/SLP-65, Vav family members and PLCgamma isoforms.