Cytokine receptors encompass receptors for various cytokines and some hormones like growth hormone and prolactin. Cytokine receptors associate with JAKs, which phosphorylate and activate STATs. These latent transcription factors then migrate to the nucleus to regulate gene transcription. Cytokine receptors are dimers or trimers and are stably associated with one or two of the four known JAKS (JAK1, JAK2, JAK3, and Tyk2). Cytokine binding brings 2 JAKs into close proximity, enabling their phosphorylation and activation. JAKs phosphorylate tyrosines on the receptor tails, creating docking sites for STATs. There are 6 STATS in mammals, Each STAT protein possesses an SH2 domain. It binds to phosphorylated receptor via this domain, allowing JAKs to phosphorylate STAT. This phosphorylation then triggers STAT dissociation from receptor. STAT's SH2 domain then mediates its binding to another phosphorylated STAT, forming homo- or heterodimers. The STAT dimer translocates to the nucleus, where it binds to specific DNA sequences, activating gene transcription.

various cytokines and some hormones like growth hormone and prolactin

JAKs, which phosphorylate and activate STATs.

migrate to the nucleus to regulate gene transcription.

dimers or trimers and are stably associated with one or two of the four known JAKs (JAK1, JAK2, JAK3, and Tyk2).

brings 2 JAKs into close proximity, enabling their phosphorylation and activation.

tyrosines on the receptor tails, creating docking sites for STATs.

6 STATS in mammals, Each STAT protein possesses an SH2 domain.

via their SH2 domain, allowing JAKs to phosphorylate STAT.

triggers STAT dissociation from the receptor.

STAT's SH2 domain mediates its binding to another phosphorylated STAT, forming homo- or heterodimers.

nucleus, where it binds to specific DNA sequences, activating gene transcription.

The TGF-beta superfamily comprises 33 structurally related, secreted dimeric proteins in humans. These proteins function as hormones or local mediators, regulating diverse biological processes in animals. During development, they control pattern formation and influence cell behaviors like proliferation, differentiation,extracellular matrix production, and cell death. In adults, they play crucial roles in tissue repair, immune regulation, and other processes. The superfamily includes the TGF-beta/activin family and the larger BMP family. TGF-beta superfamily proteins act through enzyme-coupled receptors that are single pass transmembrane proteins with a serine/threonine kinase domain on the cytosolic side of the plasma membrane. TGF-β superfamily receptors are serine/threonine kinases forming homodimers. Ligand binding brings together type-I and type-II receptor dimers, enabling type-II to phosphorylate and activate type-I, creating an active tetrameric complex. Activated type-I receptors phosphorylate Smad proteins. TGF-β/activin receptors phosphorylate Smad2/3, while BMP receptors phosphorylate Smad1/5/8. Phosphorylated R-Smads dissociates from recepotor and bind to Smad4, forming a complex with 5 R-Smads that translocates to the nucleus to regulate gene transcription. Smads shuttle between nucleus and cytoplasm, with dephosphorylation in nucleus and rephosphorylation at the receptor upon return. This dynamic regulation allows for a graded response to the extracellular signal based on both its concentration and duration.

33 structurally related, secreted dimeric proteins in humans

Hormones or local mediators

Pattern formation, cell proliferation, differentiation, extracellular matrix production, and cell death

Tissue repair and immune regulation

TGF-beta/activin family and BMP family

enzyme-coupled receptors that are single pass transmembrane proteins with a serine/threonine kinase domain on the cytosolic side of the plasma membrane.

Homodimers with a serine/threonine kinase domain

Type-II receptor phosphorylates and activates type-I receptor, forming an active tetrameric complex

phosphorylate Smad proteins

Smad2/3

Smad1/5/8

dissociates from recepotor and bind to Smad4, forming a complex with 5 R-Smads that translocates to the nucleus to regulate gene transcription.

undergo dephosphorylation in the nucleus and rephosphorylation at the receptor upon return

graded response to the extracellular signal based on concentration and duration