Complex interactions between thyroid hormone and fibroblast growth factor signalling.
OBJECTIVE
Thyroid hormone and fibroblast growth factors are critically important for normal development. Recent evidence points to complex interactions between thyroid hormone and fibroblast growth factors that regulate cell proliferation and differentiation. We discuss mechanisms of thyroid hormone and fibroblast growth factor action, and identify downstream signalling responses that offer opportunities for regulatory crosstalk.


RESULTS
Thyroid hormone action is mediated by nuclear receptors that regulate gene expression in response to thyroid hormone. Recent studies have shown thyroid hormone also acts at the cell membrane via the alpha(V)beta(3) integrin receptor and these actions also communicate with nuclear responses to thyroid hormone. Fibroblast growth factors act via receptor tyrosine kinases to stimulate second messenger pathways that also communicate with nuclear events. Several common pathways, including mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and signal transducer and activator of transcription signalling, are activated by thyroid hormone and fibroblast growth factor, and may act as points of convergence for interaction in tissues, such as bone, central nervous system and heart, as well as in the extra-cellular matrix and during angiogenesis.


CONCLUSIONS
Although there is convincing evidence that thyroid hormone and fibroblast growth factors interact widely, little is known about molecular mechanisms that determine this interplay. Future research in this expanding field may result in identification of new pharmacological targets for manipulation of cell proliferation and differentiation.
Williams
Allan J
AJ
Molecular Endocrinology Group, Division of Medicine & MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK.
O'Shea
Patrick J
PJ
Williams
Graham R
GR
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004789:Enzyme Activation; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013963:Thyroid Hormones / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014157:Transcription Factors; D005346:Fibroblast Growth Factors; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases