Modular binding domains in signal transduction proteins

Cohen, George B.; Ren, Ruibao; Baltimore, David

doi:10.1016/0092-8674(95)90406-9

Cited by 969 publications

(740 citation statements)

References 73 publications

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“…However, because AATYK does not possess any SH3 or SH2 domains which are known to mediate binding to other adaptor proteins, substrate recognition and the regulation of enzymatic activity (Koch et al, 1991;Schlessinger, 1994), it is possible that its functions are regulated in a manner which is distinct from other family members. A distinguishing feature of the amino acid sequence of AATYK is that it has several PXXP motifs which consistute the minimal binding site for other SH3 domain-containing proteins, such as Abl, Crk and Grb2 (Cohen et al, 1995). Many proteins, including Grb2, function as adaptor molecules which bring other proteins into close proximity of each other so that they can bind to substrates or become part of a larger, more intricate signaling complex (Koch et al, 1991;Schlessing, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…AATYK does not appear to contain any SH2 or SH3 domains, but the C-terminal domain was found to be very rich in proline residues. This proline-rich domain was found to contain 16 PXXP motifs, which constitutes the most conserved motif within known SH3 domain ligands (Cohen et al, 1995), suggesting that AATYK might form signaling complexes with other molecules that contain SH3 domains. These putative binding sites are underlined in Figure 3.…”

Section: Identi®cation and Molecular Cloning Of Aatykmentioning

confidence: 99%

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AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells

Gaozza

et al. 1997

Oncogene

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Section: Discussionmentioning

confidence: 99%

Section: Identi®cation and Molecular Cloning Of Aatykmentioning

confidence: 99%

AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells

Gaozza

et al. 1997

Oncogene

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“…Src homology 2 and 3 domains (SH2 and SH3) are small protein modules found in a variety of signaling proteins, which mediate protein-protein interactions in signal transduction pathways activated by protein tyrosine kinases (Pawson and Schlessinger, 1993;Cohen et al, 1995). SH2 domains bind to short phosphotyrosine containing sequences in growth factor receptors and other phosphoproteins.…”

Section: Introductionmentioning

confidence: 99%

Crk protein binds to PDGF receptor and insulin receptor substrate-1 with different modulating effects on PDGF- and insulin-dependent signaling pathways

et al. 1998

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We have studied the involvement of murine c-Crk, an SH2/SH3 containing adaptor protein, in signaling pathways stimulated by di erent receptor tyrosine kinases. We show here that c-Crk is associated with components of insulin-and PDGF-dependent signaling pathways. Insulin treatment of murine myoblast cells induces the formation of stable complex of endogenous cCrk with insulin receptor substrate-1 (IRS-1) mediated via the SH2 domain of Crk. The ligand dependent physical association of c-Crk with IRS-1 is direct. However IRS-1 is also co-precipitated with c-Crk from quiescent L6 cells. The association of IRS-1 with c-Crk in quiescent cells is probably not direct since Far Western blot analysis did not reveal the binding of neither SH2 domain nor amino-terminal SH3 domain of c-Crk to IRS-1 from unstimulated cells. We also show that PDGF treatment of murine myoblast cells induces association of c-Crk with the PDGF receptor and tyrosine phosphorylation of c-Crk. Overexpression of cCrk enhanced insulin-but not PDGF-induced activation of MAP kinases when compared to parental cell lines. Thus, the formation of the direct IRS-1/Crk complex appears to be crucial for Crk-mediated insulin-induced activation of MAP kinase, whereas Crk is probably involved in other PDGF-induced responses. These data provide support to the hypothesis that insulin and PDGF employ di erent mechanisms for activation of MAP kinase cascade.

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“…This SH3 domain shows 100 % identity with Abi-2 [27]. Several proline-rich stretches are found in THRP ( Figure 1) that constitute potential binding sites for SH3 domaincontaining proteins and contain the consensus PXXP sequence present in all high-affinity SH3 ligands [33,34]. A polyproline stretch, which could function as a transcriptional activation domain [35], is found upstream of the SH3 domain.…”

Section: Speciesmentioning

confidence: 99%

Cloning and characterization of a complementary DNA for a thyroid hormone-responsive protein in mature rat cerebral tissue

Shah

Schneiderjohn

et al. 1997

Biochemical Journal

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A gene responsive to thyroid hormone (TH) has been identified in the adult rat brain cerebral tissue. A cDNA probe differentially expressed in euthyroid, hypothyroid and hyperthyroid rat cerebral tissue, generated by reverse transcriptase-PCR differential display of mRNA, was used to screen the rat brain cDNA library. A 3.4 kb positive clone hybridized in Northern blots with a 3.8 kb mRNA that proved to be TH responsive (THR). The remaining coding sequence and a part of the 5ʹ untranslated region of this cDNA were obtained by 5ʹ rapid amplification of cDNA ends. The deduced amino acid sequence revealed that THR protein (THRP), a 68 kDa moiety, has 83% sequence similarity with c-Abl interactor protein (Abi-2), which is a substrate for tyrosine kinase activity of c-Abl. The extensive similarity between the two proteins suggests a potential role for THRP as a substrate for c-Abl. Northern analysis showed that the expression of THR mRNA in hyperthyroid rats is 6-fold that in euthyroid rats. There is also a 4-6-fold increase in the concentration of THRP, as analysed by Western analysis. Owing to the extensive similarity between rat THRP and human Abi-2, a polyclonal anti- (human Abi-2) antibody was successfully used for Western analysis of proteins from the rat tissues. The observed increase in both the mRNA and the protein did not decline after β-adrenergic system blockade with propranolol, suggesting that the action of TH on the expression of this gene is not mediated through the β-adrenergic system. Immunohistochemical studies revealed that neuronal cells were particularly rich in THRP. Both THR mRNA and THRP are rapidly induced in vivo after intravenous administration of thyroxine. Tissue distribution studies indicated that the cerebral tissue was particularly enriched with THR mRNA and 68 kDa THRP. A cDNA clone for a THR gene could provide a useful tool to study the molecular mechanisms of TH effects on cerebral tissue in adult animals.

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Modular binding domains in signal transduction proteins

Cited by 969 publications

References 73 publications

AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells

AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells

Crk protein binds to PDGF receptor and insulin receptor substrate-1 with different modulating effects on PDGF- and insulin-dependent signaling pathways

Cloning and characterization of a complementary DNA for a thyroid hormone-responsive protein in mature rat cerebral tissue

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