Exam 4 - TGFβ/Gunanylyl Cyclase R/NO&Ion CLRP Flashcards
TGFβ receptor family are also called what?
Receptor Serine/Threonine Protein Kinases
Ligands for receptor ser/thr protein kinases (TGFβ superfamily)?
A related superfamily of about 33 ligands in humans including the following subgroups:
- TGFβs (transforming growth factor βs)
- TGFβ
- inhibins
- activins
- BMPs (bone morphogenetic proteins)
- -BMPs/GDFs
- anti-Mullerian hormone (AMH, MIS)
What functions do TGFβ-related ligands perform during development?
Regulate pattern formation, influence proliferation, differentiation, tissue remodeling, and promote cell death
What functions do TGFβ-related ligands perform in adults?
Involved in cell homeostasis, tissue repair and remodeling, inhibition of cell proliferation, and immune regulation
Basically, what do members of the TGFβ subgroup of receptor ser/thr protein kinase ligands do?
Inhibition of cell proliferation
Immune system suppression
Basically, what do members of the BMP subgroup of receptor ser/thr protein kinase ligands do?
BMP (bone morphogenetic protein) subgroup:
Osteogenesis (formation of bone)
Chondrogensis (formation of cartilage)
TGFβ signalling is usually ________, but can be _______, especially in cancer
TGFβ signalling is usually paracrine, but can be autocrine, especially in cancer
How is TGFβ processed?
TGFβ superfamily members synthesised in precursor form, contain Pro-region and Mature ligand.
Two of these precursors are dimerised, each peptide chain cleaved from their respective Pro-regions, and secreted
Once secreted, the latent form remains associated with its Pro-regions and/or other interacting biologically inactive proteins
A variety of poorly-understood mechanisms remove associated proteins which results in the biologically-active form
How long is mature TGFβ?
112 amino acids long
Why is signal interpretation difficult amongst the TGFβ superfamily ligands?
Ligands in the TGFβ superfamily can heterodimerise or homodimerise during processing, and many of these peptides have similar functions and can compensate for each other, which makes understanding their precise function difficult
TGFβ superfamily signalling requires what type of receptor?
Two types of Receptor Serine/Threonine Protein Kinases (TGFβ receptor family):
Type I: phosphorylate R-Smads
Type II: bind ligand, phosphorylate Type I receptors
Receptor ser/thr protein kinase Type I
Function: phosphorylate R-Smads
Ex: ALK1, … , ALK7
Receptor ser/thr protein kinase Type II
Function: bind ligand, phosphorylate Type I receptor on GS domain
Ex: TβRII, ActRII, ActRIIB, BMPRII, MISR
What is the sequence difference between receptor ser/thr kinase (TFGβ receptor family) type I and type II?
Approximately 40% sequence identity (both are ser/thr kinases), Type I has GS domain that is phosphorylated by Type II
How do TGFβ receptors bind ligand?
TGFβ receptors and ligands are promiscuous. Each member of the TGFβ superfamily binds to a characteristic combination of type-I and type-II receptor dimers.
- The type II receptor dimer binds ligand first and then forms a complex with the type I receptor dimer.
- Both receptor subunits possess serine/threonine protein kinase activity.
- After ligand binding, the type II subunit phosphorylates a specific site (GS domain) on the type I subunit to activate its kinase activity
- The type I receptor then phosphorylates latent transcription factors known as R-Smads (receptor Smads).