Growth hormone stimulates the tyrosine phosphorylation and association of p125 focal adhesion kinase (FAK) with JAK2. Fak is not required for stat-mediated transcription.
We have demonstrated that growth hormone (GH) activates focal adhesion kinase (FAK), and this activation results in the tyrosine phosphorylation of two FAK substrates, paxillin and tensin. The activation of FAK is time-dependent (maximal activation at 5-15 min) and dose-dependent (maximal activation at 0.05 nM). FAK and paxillin are constitutively associated in the unstimulated state, remain associated during the stimulation phase, and recruit tyrosine-phosphorylated tensin to the complex after GH stimulation. Half of the carboxyl-terminal region of the GH receptor is dispensable for FAK activation, but FAK activation does require the proline-rich box 1 region of the GH receptor, indicative that FAK is downstream of JAK2. FAK associates with JAK2 but not JAK1 after GH stimulation of cells. Using FAK-replete and FAK-deficient cells, we also show that FAK is not required for STAT-mediated transcriptional activation by GH. The use of FAK in the signal transduction pathway utilized by GH may be central to many of the pleiotropic effects of GH, including cytoskeletal reorganization, cell migration, chemotaxis, mitogenesis, and/or prevention of apoptosis and gene transcription.
Zhu
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Institute of Molecular and Cell Biology and Defense Medical Research Institute, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Republic of Singapore.
Goh
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Lobie
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D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D053614:Janus Kinase 2; D008894:Milk Proteins; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D014443:Tyrosine / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C496050:PTK2 protein, human