Src family protein tyrosine kinases and cellular signal transduction pathways

Erpel, Thorsten; Courtneidge, Sara A.

doi:10.1016/0955-0674(95)80025-5

Cited by 278 publications

(175 citation statements)

References 71 publications

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“…Both Ret and Src kinases can phosphorylate Fak in vitro (Erpel & Courtneidge, 1995; Plaza‐Menacho et al , 2011). In the context of gain‐of‐function Ret mutations, different studies have reached opposite conclusions regarding the ability of Fak to enhance or suppress Ret‐driven neoplasia (Panta et al , 2004; Plaza‐Menacho et al , 2011; Sandilands et al , 2012; Macagno et al , 2014).…”

Section: Resultsmentioning

confidence: 99%

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

et al. 2017

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Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homeostatic contexts. They also suggest an epithelial contribution to Ret loss‐of‐function disorders such as Hirschsprung disease.

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Section: Resultsmentioning

confidence: 99%

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

et al. 2017

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“…Src is implicated in a variety of cellular processes and plays a prominent role in the regulation of the actin-based cortical cell cytoskeleton (3,40). In PC12 cells, enhanced expression of Src induced nerve-growth-factor-independent neurite outgrowth (41).…”

Section: Discussionmentioning

confidence: 99%

Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity

Onofri

Giovedì

Vaccaro

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Synapsin I is a synaptic vesicle-associated phosphoprotein that has been implicated in the formation of presynaptic specializations and in the regulation of neurotransmitter release. The nonreceptor tyrosine kinase c-Src is enriched on synaptic vesicles, where it accounts for most of the vesicle-associated tyrosine kinase activity. Using overlay, affinity chromatography, and coprecipitation assays, we have now shown that synapsin I is the major binding protein for the Src homology 3 (SH3) domain of c-Src in highly purified synaptic vesicle preparations. The interaction was mediated by the proline-rich domain D of synapsin I and was not significantly affected by stoichiometric phosphorylation of synapsin I at any of the known regulatory sites. The interaction of purified c-Src and synapsin I resulted in a severalfold stimulation of tyrosine kinase activity and was antagonized by the purified c-Src-SH3 domain. Depletion of synapsin I from purified synaptic vesicles resulted in a decrease of endogenous tyrosine kinase activity. Portions of the total cellular pools of synapsin I and Src were coprecipitated from detergent extracts of rat brain synaptosomal fractions using antibodies to either protein species. The interaction between synapsin I and c-Src, as well as the synapsin I-induced stimulation of tyrosine kinase activity, may be physiologically important in signal transduction and in the modulation of the function of axon terminals, both during synaptogenesis and at mature synapses.Synapsin I is the major synaptic vesicle protein that binds to the Src homology 3 (SH3) domains of the adapter protein Grb2 in vitro (1). This interaction is mediated by domain D of synapsin I, a 23-kDa proline-rich, strongly basic domain located in the COOH-terminal portion of synapsin I (2). It seemed possible that domain D or other proline-rich regions in synapsin I might interact with other SH3 domain-containing proteins within the nerve terminal and that these interactions might have a physiological role in presynaptic function. One such candidate, the SH3 domain-containing nonreceptor tyrosine kinase c-Src, is expressed at high levels in postmitotic neurons and is enriched on synaptic vesicles, where it accounts for most of the vesicle-associated tyrosine kinase activity (3-6). Using purified components in vitro, we now report that a domain Dmediated interaction of synapsin I with the SH3 domain of c-Src results in a 5-fold activation of the catalytic activity of c-Src. We also present studies employing a variety of biochemical techniques that serve to further characterize the specificity, subcellular location, regulation, and potential functional consequences of the c-Src͞synapsin I interaction.

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“…These kinases have been suggested to play diverse roles in cell proliferation, differentiation, survival, and death (5,8,22,32,39,41). Among these four families, the Bruton's tyrosine kinase (Btk) family is unique in that the kinases in this family have extended N-terminal sequences that are called collectively the pleckstrin homology (PH) domain (17,18).…”

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confidence: 99%

The Drosophila Bruton’s Tyrosine Kinase (Btk) Homolog Is Required for Adult Survival and Male Genital Formation

Baba

Takeshita

Majima

et al. 1999

Molecular and Cellular Biology

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We isolated a Drosophila fickle P (fic P ) mutant with a shortened copulatory duration and reduced adult-stage life span. The reduced copulatory duration is ascribable to incomplete fusion of the left and right halves of the apodeme that holds the penis during copulation. fic P is an intronic mutation occurring in the Btk gene, a gene which encodes two forms (type 1 and type 2) of a Bruton's tyrosine kinase (Btk) family cytoplasmic tyrosine kinase as a result of alternative exon usage. The fic P mutation prevents the formation of the type 2 isoform but leaves expression of the type 1 transcript intact. Ubiquitous overexpression of the wild-type cDNA by using a heat shock 70 promoter during the late larval or pupal stages rescued the life span and genital defects in the mutant, respectively, establishing the causal relationship between the fic P phenotypes and the Btk gene mutation. The stage specificity of the rescuing ability suggests that the Btk gene is required for the development of male genitalia and substrates required for adult survival.

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Src family protein tyrosine kinases and cellular signal transduction pathways

Cited by 278 publications

References 71 publications

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia

Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity

The Drosophila Bruton’s Tyrosine Kinase (Btk) Homolog Is Required for Adult Survival and Male Genital Formation

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