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Platelet-derived growth factor (PDGF)-induced activation of signal transducer and activator of transcription (Stat) 5 is mediated by PDGF beta-receptor and is not dependent on c-src, fyn, jak1 or jak2 kinases.

ABSTRACT: Several growth factors activate signal transducers and activators of transcription (Stats) but the mechanism of Stat activation in receptor tyrosine kinase signalling has remained elusive. In the present study we have analysed the roles of different platelet-derived growth factor (PDGF)-induced tyrosine kinases in the activation of Stat5. Co-expression experiments in insect and mammalian cells demonstrated that both PDGF beta-receptor (PDGF beta-R) and Jak1, but not c-Src, induced the activation of Stat5. Furthermore, immune-complex-purified PDGF beta-R was able to phosphorylate Stat5 directly. The role of the cytoplasmic tyrosine kinases in the PDGF-induced activation of Stat5 was further investigated by overexpressing kinase-negative (KN) and wild-type Jak and c-Src kinases. Jak1-KN or Jak2-KN had no effect but both Src-KN and wild-type c-Src similarly decreased the PDGF-beta-R-induced activation of Stat5. The activation of both Src and Stat5 is dependent on the same tyrosine residues Tyr(579) and Tyr(581) in PDGF beta-R; thus the observed inhibition by Src might result from competition for binding of Stat5 to the receptor. Finally, fibroblasts derived from Src(-/-) and Fyn(-/-) mice showed normal pattern of PDGF-induced tyrosine phosphorylation of Stat5. Taken together, these results indicate that Stat5 is a direct substrate for PDGF beta-R and that the activation does not require Jak1, Jak2, c-Src or Fyn tyrosine kinases.

SUBMITTER: Paukku K

PROVIDER: S-EPMC1220814 | biostudies-other | 2000 Feb

REPOSITORIES: biostudies-other

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Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn.

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2007-09-22 | E-GEOD-2196 | biostudies-arrayexpress

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Genes induced by PDGF-BB in cells lacking Signal Transducer and Activator of Transcription-1 (Stat1)

Project description:Comparison of gene expression between Stat1+/- and Stat1-/- dermal fibroblasts or vascular smooth muscle cells after treatment with PDGF-BB for one hour.

2020-06-13 | GSE152342 | GEO

Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells.

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| S-EPMC3671957 | biostudies-literature

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| S-EPMC2984176 | biostudies-literature

Genome-wide binding signature of Signal transducer and activator of transcription (STAT) family in colorectal cancer HCT 116 cell

Project description:The excessive and continuous activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway leads to the proliferation and migration of malignant cells resulting in the occurrence and development of almost all of cancers. The defined gene sets specifically activated by different STAT proteins are relied on their genomic accessibility by the interplay of certain STAT proteins with other potential cofactors. However, we have no clue about the status of human activated STAT dimers in the nucleus, as well as the intercrossing modules of synergic, supplementary or competitive relationship among each other in colorectal cancer. In current study, chromatin immunoprecipitation sequencing (ChIP-seq) was conducted to explore the genome-scale binding signatures of STAT1, STAT2, STAT3, STAT5A/B and STAT6 in human HCT-116 CRC cells. Moreover, STAT3 binding on genomic DNA was also investigated in HCT116 cells with NR5A2 knockdown.

2021-11-08 | E-MTAB-11113 | biostudies-arrayexpress

Rescue of a trafficking defective human pacemaker channel via a novel mechanism: roles of Src, Fyn, and Yes tyrosine kinases.

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