Paracrine signaling

In fact, different organs in the body - even between different species - are known to utilize a similar sets of paracrine factors in differential development.

Binding of a paracrine factor to its respective receptor initiates signal transduction cascades, eliciting different responses.

Although the FGF family of paracrine factors has a broad range of functions, major findings support the idea that they primarily stimulate proliferation and differentiation.

[2][3] To fulfill many diverse functions, FGFs can be alternatively spliced or even have different initiation codons to create hundreds of different FGF isoforms.

Each pathway leads to the activation of transcription factors which enter the nucleus to alter gene expression.

In fact, mutant forms of a single RTK may play a causal role in very different types of cancer.

Mutant forms of the Kit receptor, which fire constitutively in a ligand-independent fashion, are found in a diverse array of cancerous malignancies.

[11] Research on thyroid cancer has elucidated the theory that paracrine signaling may aid in creating tumor microenvironments.

[12] Effectively, multiple bindings of ligands to the RTK receptors overstimulates the Ras-Raf-MAPK pathway, which overexpresses the mitogenic and invasive capacity of cells.

The STAT proteins dimerize and enter the nucleus to act as transcription factors to alter gene expression.

[17] This is due to a mutation in a Fgf gene, causing a premature and constitutive activation of the Stat1 transcription factor.

[18] Research on paracrine signaling through the JAK-STAT pathway revealed its potential in activating invasive behavior of ovarian epithelial cells.

[20] The Hedgehog protein family is involved in induction of cell types and the creation of tissue boundaries and patterning and are found in all bilateral organisms.

Hedgehog proteins produce key signals for the establishment of limb and body plan of fruit flies as well as homeostasis of adult tissues, involved in late embryogenesis and metamorphosis.

Sonic hedgehog (SHH) has various roles in vertebrae development, mediating signaling and regulating the organization of central nervous system, limb, and somite polarity.

Indian hedgehog (IHH) is expressed in the gut and cartilage, important in postnatal bone growth.

Inhibition of Smoothened causes the Cubitus interruptus (Ci), Fused, and Cos protein complex attached to microtubules to remain intact.

[23][24][25] The Hedgehog Signaling pathway is critical in proper tissue patterning and orientation during normal development of most animals.

Aberrant activation of the Hedgehog pathway has been implicated in several types of cancers, Basal Cell Carcinoma in particular.

In addition, therapy-induced Hedgehog pathway activation has been shown to be necessary for progression of Prostate Cancer tumors after androgen deprivation therapy.

IP3 can then bind to a receptor on the endoplasmic reticulum to release intracellular calcium stores, to induce calcium-dependent gene expression.

Mutations that cause constitutive activation of the Wnt signaling pathway lead to tumor formation and cancer.

Current research is focused on the action of the Wnt signaling pathway the regulation of stem cell choice to proliferate and self renew.

[34][35][36] "TGF" (Transforming Growth Factor) is a family of proteins that includes 33 members that encode dimeric, secreted polypeptides that regulate development.

[37] Many developmental processes are under its control including gastrulation, axis symmetry of the body, organ morphogenesis, and tissue homeostasis in adults.

[39] The TGF-β pathway regulates many cellular processes in developing embryo and adult organisms, including cell growth, differentiation, apoptosis, and homeostasis.

The R-SMAD/Co-SMAD forms a complex with importin and enters the nucleus, where they act as transcription factors and either up-regulate or down-regulate in the expression of a target gene.

[39] TGF-β proteins regulate epithelia by controlling where and when they branch to form kidney, lung, and salivary gland ducts.

The local action of growth factor signaling plays an especially important role in the development of tissues.

Also, retinoic acid, the active form of vitamin A, functions in a paracrine fashion to regulate gene expression during embryonic development in higher animals.

Overview of signal transduction pathways.
Diagram showing key components of a signal transduction pathway. See the MAPK/ERK pathway article for details.
Production of the CiR transcriptional repressor when Hh is not bound to Patched. In the diagram, "P" represents phosphate .
When Hh is bound to Patched (PTCH), Ci protein is able to act as a transcription factor in the nucleus.
Figure of the three main pathways of Wnt signaling in biological signal transduction.
Canonical Wnt pathway without Wnt.
Noncanonical Wnt Planar Cell Polarity pathway.
Noncanonical Wnt/calcium pathway.
SMAD Signaling Pathway Activated by TGF-β