| ||INVOLVEMENT OF INTRACELLULAR & MEMBRANE ASOCIATED TEMs IN POLICING STEPS OF ANGIOGENESIS|| |
|general context signaling |
- G-protein signaling:
- small GTPases:
- Secretin family receptor (TEM9)
- RGS (PEM24= TEM42= RGS5)
- Ras family small GTPases (TEM2)
- TEM9 is a previously non-decribed seven-transmembrane domain protein belonging to the secretin receptor family. Proteins with closest similarity in their transmembrane region are involved in cytoskeletal rearrangments.
- RGS5 (TEM42) is a G-protein signaling regulator of unknown specificity that was shown to be expressed differentially in artery versus vein media.
- TEM2 is a ras superfamily and rap subfamily member. The likely rat orthologue Rhes shows thyroid hormone dependent expression, and thus, might show a functional and/or causal linkage with Dkk-3 (TEM4) expression.
- Connexin45 (TEM35) was recently and unexpectedly found to be essential for vascular development in a Cx45 deficiency study.
- HEYL (TEM8= PEM68) encodes a basic helix-loop-helix transcription factors related to the hairy/Enhancer of split genes. The protein TEM8 (HEYL) is likely to act by dimerizing with other bHLH proteins, potentially with members of the same family. A function for Hairy/E(SPL) transcription factors in angiogenesis is well established. HeyL transcription is potentially regulated by Notch.
|INVOLVEMENT OF INTRACELLULAR & MEMBRANE ASOCIATED TEMs IN EXECUTIVE STEPS OF ANGIOGENESIS AND THEIR REGULATION|
|cytoskeletal remodeling & related signaling
- (Tropomyosin= TEM45)
- TEM5 is a previously non-decribed RhoGEF could act upstream of Rho family members in regulating the behaviour of cytoskeletal and structural proteins. TEM5 might have an integrative function between Rho-GTPase signaling and MAPK-pathways (JNK and/or ERK-cascade), and might interact with SH3 domain containing and/or 14-3-3 proteins.
- TEM16 is highly similar to tensins. If it is assumed that TEM16 is a fragment of a complete tensin, functions typical for tensins might be hypothesized for the protein.
- TEM24, the recently cloned human tensin, has a proposed integrative function for signal transductions with the cytoskeleton. It localizes to the focal adhesion where it binds both actin filaments and tyrosine-phosphorylated proteins. The mechanism of a proposed JNK regulation remains unclear. A functional link between TEM5 and TEM24 is not excluded since 89% of the Unigen SAGE libraries with TEM24 upregulation show expression of TEM5 as well.
- TEM28 is a previously non-decribed RhoGAP that might act upstream of Rho family members. Via its N-terminal coiled-coil and a C-terminal SH3-domain binding proline-rich region, it could mediate signalling between membrane receptors, the cytoskeleton and the nucleus.
- Integrin alpha1= TEM30
- Thy-1= TEM13
- Thy-1 (TEM13) is a GPI-anchored protein having a role in the regulation of cell-cell adhesion and differentiation.
- TEM17 is a potential type I membrane protein. In its extracellular domain, Tem17 shares regions of similarity to nidogen and plexins, two protein-families which have been implicated in axon migration.
- Integrin alpha1 (TEM30) binds collagens I, collagen IV, laminin and mediates migration on collagen. It is involved in regulating collagen and MMP synthesis.
|endo- and exocytosis|
- Endosialin= TEM1
- uPARAP= TEM22
- Peanut-like= TEM46
- Given the similarity of the receptor endosialin (TEM1) to C1qR and the existence of the WIGL motif, a function in internalization can be proposed.
- uPARAP (TEM22) is an endocytic recycling glycoprotein belonging to the macrophage mannose receptor family. The protein has been found to bind strongly to collagenV and participate in a tri-molecular complex with the urokinase receptor and pro-urokinase. It has been hypothesized that the protein might be involved in the uptake of highly glycosylated proteins in the course of matrix remodelling.
- Peanut-like 1 (TEM46) is a septin that associates with synaptic vesicles. It is hypothesized to have both a positive and a negative role in exocytosis.
- protein fragment of an extracellular domain containing protein (TEM19)
- undetermined protein sequences (TEM3, TEM18, TEM26, TEM29, TEM32, TEM33, TEM34, TEM43, TEM44)