PTP1D is a positive regulator of the prolactin signal leading to beta-casein promoter activation.
Stimulation of the prolactin receptor (PRLR), a member of the cytokine/growth hormone receptor family, results in activation of the associated Jak2 tyrosine kinase and downstream signaling pathways. We report that PTP1D, a cytoplasmic protein tyrosine phosphatase containing two Src homology 2 (SH2) domains, physically associates with the PRLR-Jak2 complex and is tyrosine-phosphorylated upon stimulation with prolactin. The formation of the trimeric PRLR-Jak2-PTP1D complex is critical for transmission of a lactogenic signal, while PTP1D phosphorylation is necessary, but not sufficient. The dominant negative inhibitory effect of a phosphatase-deficient mutant on expression of a beta-casein promoter-controlled reporter gene is evidence for an essential role of fully functional PTP1D in the regulation of milk protein gene transcription.
Ali
S
S
Department of Molecular Biology, Max-Planck-Institut fur Biochemie, Martinsried, Germany.
Chen
Z
Z
Lebrun
J J
JJ
Vogel
W
W
Kharitonenkov
A
A
Kelly
P A
PA
Ullrich
A
A
D001483:Base Sequence; D002364:Caseins / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D008969:Molecular Sequence Data; D019000:Phosphotyrosine / Q000378:metabolism; D011388:Prolactin / Q000502:physiology*; D011401:Promoter Regions, Genetic; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin / Q000502:physiology*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D018909:src Homology Domains
D002364:Caseins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D019000:Phosphotyrosine; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases