p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity.

Lioubin, Mario N.; Algate, Paul A.; Tsai, Schickwann; Carlberg, Kristen; Aebersold, A; Rohrschneider, Larry R.

doi:10.1101/gad.10.9.1084

Cited by 403 publications

(396 citation statements)

References 55 publications

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“…After Western blot, proteins were revealed with anti SOS (which recognizes both SOS1 and 2), anti myc and anti FLT4 antibodies FLT4L interferes only with the formation of FLT4L-SHC complex whereas overexpression of SHC PTB protein probably competes the binding of SHC with FLT4L but also with other proteins. For example, a likely target of SHC PTB domain is SHIP, a phosphatidylinositol phosphatase that inhibits the signaling mediated by Insulin and immune receptors like FcgRIIB (Lioubin et al, 1996;Ono et al, 1996;Deuter-Reinhard et al, 1997). The expression of SHC PTB construct may disrupt the pool of SHIP-SHC complex and interfere with the inhibitory signaling of SHIP.…”

Section: Discussionmentioning

confidence: 99%

Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF Receptor 3 signaling

et al. 1999

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The VEGFR3/FLT4 receptor, which is involved in vasculogenesis and angiogenesis, binds and phosphorylates SHC proteins on tyrosine residues. SHC contains two phosphotyrosine interaction domains: a PTB (Phosphotyrosine Binding) and a SH2 (Src Homology 2) domain. Previous studies have shown that SHC proteins are phosphorylated on Y239/Y240 and Y313 (Y317 in humans) by tyrosine kinases such as the EGF and IL3 receptors. We have investigated which of the SHC tyrosine residues are targeted by the VEGFR3/ FLT4 kinase and the role of the SHC PTB and SH2 domains in this process. Our results show that Y239/ Y240 and Y313 are simultaneously phosphorylated by the kinase, creating GRB2 binding sites. Mutation of SHC PTB, but not SH2, domain interferes with the SHC phosphorylation by VEGFR3/FLT4. Soft agar assay experiments revealed that the VEGFR3/FLT4 transforming capacity is increased by the mutation of Y239/Y240 to phenylalanines in SHC, suggesting that these two residues mediate an inhibitory signal for cell growth. Mutation of the two phosphorylation sites increases this e ect, suggesting that they have a synergistic role.

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Section: Discussionmentioning

confidence: 99%

Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF Receptor 3 signaling

et al. 1999

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“…IL-3 stimulation also results in tyrosine phosphorylation of the inositol phosphatase (SHIP) which forms a complex with Shc, Grb2 and Sos, which are members of the Ras pathway (Lioubin et al, 1996). Upon recruitment, Shc binds to the phosphorylated Y577 of the b c subunit and subsequently interacts with the adaptor protein Grb2, which in turn associates with mSos, which is the nucleotide exchange factor for Ras (Pratt et al, 1996;Rozakis-Adcock et al, 1993).…”

Section: Shc-ras-map Kinase Pathwaymentioning

confidence: 99%

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

et al. 2000

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Hematopoiesis is the cumulative result of intricately regulated signal transduction cascades that are mediated by cytokines and their cognate receptors. Proper culmination of these diverse signaling pathways forms the basis for an orderly generation of di erent cell types and aberrations in these pathways is an underlying cause for diseases such as cancer. Over the past several years, downstream events initiated upon cytokine/ growth factor stimulation have been a major focus of biomedical research. As a result, several key concepts have emerged allowing a better understanding of the complex signaling processes. A group of novel transcription factors, termed signal transducers and activators of transcription (STATs) appear to orchestrate the downstream events propagated by cytokine/growth factor interactions with their cognate receptors. Until recently, the JAK proteins were considered to be the tyrosine kinases, which dictated the levels of phosphorylation and activation of STAT proteins, forming the basis of the JAK-STAT model. However, over the past few years, increasing evidence has accumulated which indicates that at least some of the STAT protein activation may be mediated by members of the Src gene family following cytokine/growth factor stimulation. Studies have demonstrated that the Src-family of tyrosine kinases can phosphorylate and activate certain STAT proteins, in lieu of JAK kinases. In such a scenario, JAK kinases may be more crucial to phosphorylation of the cytokine/growth factor receptors and in the process create docking sites on the receptors for binding of SH2-containing proteins such as STATs, Src-kinases and other signaling intermediates. Tyrosine phosphorylation and activation of STAT proteins can be achieved either by JAKs or Src-kinases depending on the nature of STAT that is being activated. This forms the basis for the JAK-Src-STAT model proposed in this review. The concerted action of JAK kinases, members of the Src-kinase family and STAT proteins, leads to cell proliferation and cell survival, the end-point of the cytokine/growth factor stimulus.

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“…A novel role for Shc has been suggested in which phosphorylation of Y239/Y240 leads to c-myc induction and suppression of apoptosis in Ba/F3 cells, in a Ras-independent manner (Gotoh et al, 1996). The Shc PTB domain binds directly to the cytoplasmic enzyme SHIP, an SH2 domain-containing inositol 5-phosphatase, in response to growth factor and cytokine stimulation in hematopoetic cells (Damen et al, 1996;Kavanaugh et al, 1996;Lioubin et al, 1996). Furthermore, proline-rich sequences in the Shc CH1 domain are proposed to mediate the interaction between Shc and the SH3 domain of eps8, a tyrosinephosphorylated protein involved in EGF receptormediated signaling (Matoskova et al, 1995;Bon®ni et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Cloning and characterization of mPAL, a novel Shc SH2 domain-binding protein expressed in proliferating cells

1999

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p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity.

Cited by 403 publications

References 55 publications

Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF Receptor 3 signaling

Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF Receptor 3 signaling

IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled

Cloning and characterization of mPAL, a novel Shc SH2 domain-binding protein expressed in proliferating cells

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